130 results on '"Delaby C."'
Search Results
2. Overview of the blood biomarkers in Alzheimer's disease: Promises and challenges
- Author
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Delaby, C., Hirtz, C., and Lehmann, S.
- Published
- 2023
- Full Text
- View/download PDF
3. Iron deficiency during first-line chemotherapy in metastatic cancers: a prospective epidemiological study
- Author
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Saint, Angélique, Viotti, J., Borchiellini, D., Hoch, B., Raimondi, V., Hebert, C., Largillier, R., Evesque, L., Follana, P., Ferrero, J. M., Delaby, C., Schiappa, R., Chamorey, E., and Barriere, J.
- Published
- 2020
- Full Text
- View/download PDF
4. Proteinopathies: molecular mechanisms and diagnostic perspectives
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Delaby, C. and Lehmann, S.
- Published
- 2022
- Full Text
- View/download PDF
5. Diagnosis associated with Tau higher than 1200 pg/mL: Insights from the clinical and laboratory practice
- Author
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Lehmann, S., Paquet, C., Malaplate-Armand, C., Magnin, E., Schraen, S., Quillard-Muraine, M., Bousiges, O., Delaby, C., Dumurgier, J., Hugon, J., Sablonnière, B., Blanc, F., Wallon, D., Gabelle, A., Laplanche, J.L., Bouaziz-Amar, E., and Peoc'h, K.
- Published
- 2019
- Full Text
- View/download PDF
6. Correction to: Proteinopathies: molecular mechanisms and diagnostic perspectives
- Author
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Delaby, C. and Lehmann, S.
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- 2022
- Full Text
- View/download PDF
7. Biomarkers of Alzheimer's disease: The present and the future
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Lehmann, S., Delaby, C., Touchon, J., Hirtz, C., and Gabelle, A.
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- 2013
- Full Text
- View/download PDF
8. Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview
- Author
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Delaby, C., Teunissen, C.E., Blennow, K., Alcolea, D., Arisi, I., Amar, E.B., Beaume, A., Bedel, A., Bellomo, G., Bigot-Corbel, E., Bjerke, M., Blanc-Quintin, M.C., Boada, M., Bousiges, O., Chapman, M.D., DeMarco, M.L., D'Onofrio, M., Dumurgier, J., Dufour-Rainfray, D., Engelborghs, S., Esselmann, H., Fogli, A., Gabelle, A., Galloni, E., Gondolf, C., Grandhomme, F., Grau-Rivera, O., Hart, M., Ikeuchi, T., Jeromin, A., Kasuga, K., Keshavan, A., Khalil, M., Körtvelyessy, P., Kulczynska-Przybik, A., Laplanche, J.L., Lewczuk, P., Li, Q.X., Lleó, A., Malaplate, C., Marquié, M., Masters, C.L., Mroczko, B., Nogueira, L., Orellana, A., Otto, M., Oudart, J.B., Paquet, C., Paoletti, F.P., Parnetti, L., Perret-Liaudet, A., Peoc'h, K., Poesen, K., Puig-Pijoan, A., Quadrio, I., Quillard-Muraine, M., Rucheton, B., Schraen, S., Schott, J.M., Shaw, L.M., Suárez-Calvet, M., Tsolaki, M., Tumani, H., Udeh-Momoh, C.T., Vaudran, L., Verbeek, M.M., Verde, F., Vermunt, L., Vogelgsang, J., Wiltfang, J., Zetterberg, H., Lehmann, S., Delaby, C., Teunissen, C.E., Blennow, K., Alcolea, D., Arisi, I., Amar, E.B., Beaume, A., Bedel, A., Bellomo, G., Bigot-Corbel, E., Bjerke, M., Blanc-Quintin, M.C., Boada, M., Bousiges, O., Chapman, M.D., DeMarco, M.L., D'Onofrio, M., Dumurgier, J., Dufour-Rainfray, D., Engelborghs, S., Esselmann, H., Fogli, A., Gabelle, A., Galloni, E., Gondolf, C., Grandhomme, F., Grau-Rivera, O., Hart, M., Ikeuchi, T., Jeromin, A., Kasuga, K., Keshavan, A., Khalil, M., Körtvelyessy, P., Kulczynska-Przybik, A., Laplanche, J.L., Lewczuk, P., Li, Q.X., Lleó, A., Malaplate, C., Marquié, M., Masters, C.L., Mroczko, B., Nogueira, L., Orellana, A., Otto, M., Oudart, J.B., Paquet, C., Paoletti, F.P., Parnetti, L., Perret-Liaudet, A., Peoc'h, K., Poesen, K., Puig-Pijoan, A., Quadrio, I., Quillard-Muraine, M., Rucheton, B., Schraen, S., Schott, J.M., Shaw, L.M., Suárez-Calvet, M., Tsolaki, M., Tumani, H., Udeh-Momoh, C.T., Vaudran, L., Verbeek, M.M., Verde, F., Vermunt, L., Vogelgsang, J., Wiltfang, J., Zetterberg, H., and Lehmann, S.
- Abstract
Item does not contain fulltext, INTRODUCTION: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. METHODS: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. RESULTS: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. DISCUSSION: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.
- Published
- 2022
9. The A beta 1-42/A beta 1-40 ratio in CSF is more strongly associated to tau markers and clinical progression than A beta 1-42 alone
- Author
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Delaby, C, Estelles, T, Zhu, NU, Arranz, J, Barroeta, I, Carmona-Iragui, M, Illan-Gala, I, Santos-Santos, MA, Altuna, M, Sala, I, Sanchez-Saudinos, MB, Videla, L, Valldeneu, S, Subirana, A, Tondo, M, Blanco-Vaca, F, Lehmann, S, Belbin, O, Blesa, R, Fortea, J, Lleo, A, and Alcolea, D
- Subjects
Amyloid ,A beta 1-40 ,Cerebrospinal fluid ,A beta 1-42 ,Tau ,Biomarkers - Abstract
Background: Cerebrospinal fluid (CSF) A beta 1-42 levels and the A beta 1-42/A beta 1-40 ratio are markers of amyloid pathology, but previous studies suggest that their levels might be influenced by additional pathophysiological processes. Aims: To compare A beta 1-42 and the A beta 1-42/A beta 1-40 ratio in CSF in different neurodegenerative disorders and study their association with other biomarkers (tTau, pTau181, and NfL) and with cognitive and functional progression. Methods: We included all participants from the Sant Pau Initiative on Neurodegeneration (SPIN) with CSF A beta 1-42 and A beta 1-42/A beta 1-40. Participants had diagnoses of Alzheimer's disease (AD), dementia with Lewy bodies, frontotemporal lobar degeneration-related syndromes, non-neurodegenerative conditions, or were cognitively normal. We classified participants as"positive" or"negative" according to each marker. We compared CSF levels of tTau, pTau181, and NfL between concordant and discordant groups through ANCOVA and assessed differences in cognitive (MMSE, FCSRT) and functional (GDS, CDR-SOB) progression using Cox regression and linear-mixed models. Results: In the 1791 participants, the agreement between A beta 1-42 and A beta 1-42/A beta 1-40 was 78.3%. The A beta 1-42/A beta 1-40 ratio showed a stronger correlation with tTau and pTau181 than A beta 1-42 and an agreement with tTau and pTau181 of 73.1% and 77.1%, respectively. Participants with a low A beta 1-42/A beta 1-40 ratio showed higher tTau and pTau181 and worse cognitive and functional prognosis, regardless of whether they were positive or negative for A beta 1-42. The results were consistent across stages, diagnostic categories, and use of different cutoffs. Conclusion: Although A beta 1-42 and A beta 1-42/A beta 1-40 are considered markers of the same pathophysiological pathway, our findings provide evidence favoring the use of the A beta 1-42/A beta 1-40 ratio in clinical laboratories in the context of AD.
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- 2022
10. Tau protein in cerebrospinal fluid: a novel biomarker of the time of death?
- Author
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Peyron, PA, Hirtz, C, Baccino, E, Ginestet, N, Tiers, L, Martinez, AY, Lehmann, S, and Delaby, C
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Cerebrospinal fluid ,Phosphorylated tau ,Post-mortem interval ,Tau protein ,Biochemistry ,Forensic pathology - Abstract
Background Tau proteins are recognized biomarkers of neurodegeneration and neuronal damage in the cerebrospinal fluid (CSF). It has also been suggested that these CSF proteins could increase post-mortem due to neuronal death. The aim of this study was to investigate the changes in CSF total and phosphorylated tau (p-tau) levels in the early post-mortem interval (PMI), to determine whether these proteins could be relevant biomarkers of time since death. Methods Tau and p-tau levels were measured by ELISA in lumbar and cisternal CSF samples from 82 corpses (46 men, 36 women, mean age: 72.4 +/- 15.2 years) with a PMI < 12 h. Forty-eight of them were considered neurologically healthy at the time of death. Rectal and tympanic temperatures were also measured in 37 individuals, and two validated temperature-based methods of PMI estimation were applied (Henssge's nomogram and Baccino's method). Results CSF tau and p-tau levels were significantly increased, with respective median values of 3315 pg/mL and 68.5 pg/mL in the whole cohort, while lower but still increased levels were observed in neurologically healthy patients. Sub-occipital punctures systematically provided higher tau and p-tau values (p < 0.0001). Despite a great inter-individual variability, the concentrations of both biomarkers were positively correlated with the early PMI, with the highest correlation for cisternal p-tau (r = 0.50, p < 0.0001 in the whole cohort; r = 0.58, p = 0.0003 in the neurologically healthy patients). Higher levels of CSF biomarkers were observed for PMI > 6 h versus PMI 6 h), with a Se of 83% and a Sp of 100% (AUC = 0.95). Conclusion Our findings suggest that CSF tau and p-tau proteins could serve as potential biomarkers of time since death, in association with tympanic temperature. The practical applicability of such an integrated approach has to be assessed by further studies.
- Published
- 2021
11. Analytical comparison of ELISA and mass spectrometry for quantification of serum hepcidin in critically ill patients
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Delaby, C, Vialaret, J, Hirtz, C, Lefebvre, T, Herkert, M, Puy, H, Lasocki, S, and Lehmann, S
- Subjects
ELISA ,hepcidin ,anemia ,mass spectrometry - Abstract
Aim: To compare methods of quantifying serum hepcidin (based on MS and ELISA) and their ability to diagnose true iron deficiency anemia in critically ill patients. Materials & methods: Serum hepcidin was measured in 119 critically ill patients included in the HEPCIDANE clinical trial, using either an ultra-sensitive ELISA kit (from DRG) or two different MS methods. Results: The results show a good correlation between the different methods studied. The Bland-Altman analysis and the Kappa test for clinical groups show a good or very good agreement between the different tests. Conclusion: ELISA or MS show a satisfactory commutability to quantify serum hepcidin. This is of great importance for the determination of therapeutic strategies in iron deficiency.
- Published
- 2021
12. Cytokines as new biomarkers of skin wound vitality
- Author
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Peyron, PA, Colomb, S, Becas, D, Adriansen, A, Gauchotte, G, Tiers, L, Marin, G, Lehmann, S, Baccino, E, Delaby, C, and Hirtz, C
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Immunoassay ,integumentary system ,Wound ,Cytokines ,Vitality ,Immunohistochemistry ,Forensic pathology - Abstract
Background The diagnosis of skin wound vitality is currently based on standard histology, but histological findings lack sensitivity in case of a short survival time. New reliable biomarkers of vitality are therefore strongly needed. We assessed the ability of 10 candidate cytokines (IFN-gamma, IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-alpha) to discriminate between vital and early post-mortem wounds. Methods Twenty-four cadavers with a recent open skin wound (< 3 h) were included (20 men, 4 women, mean age = 51.0 +/- 24.3 years). An early post-mortem wound was performed in an uninjured skin area, and both wounds were sampled at the autopsy (post-mortem interval (PMI) = 66.3 +/- 28.3 h). Needle-puncture sites related to resuscitation cares were included as very early post-mortem wounds (n = 6). In addition to standard histology, cytokines levels were simultaneously measured in each sample using a multiplex sandwich immunoassay, then normalized on healthy skin levels. A quantitative evaluation of IL-8-positive cells in ante- and post-mortem wound samples was also performed. Results In the training set of samples (n = 72), cytokine levels were significantly higher in vital wounds (mean age = 47 +/- 53 min) than in post-mortem wounds (mean PMI = 6.9 +/- 9.0 h) (p < 0.2), except for two cytokines (IFN-gamma and IL-2). IL-8 was the best discriminatory cytokine (Se = 54%, Sp = 100%, AUC = 0.79), while a multivariate model combining IL-4 and IL12p70 was a bit more discriminant (Se = 55%, Sp = 100%, AUC = 0.84). In the validation set (n = 72), the discriminatory power of the cytokines and the predictive model was slightly lower, with IL-8 remaining the best cytokine (Se = 46%, Sp = 96%, AUC = 0.75). The predictive model remained highly specific (Sp = 100%). Both the cytokines and the predictive model allowed the iatrogenic injuries to be correctly classified as post-mortem wounds. Standard histology and immunohistochemistry showed 21% sensitivity and a specificity of 79% and 100%, respectively. Only two iatrogenic wounds could be properly categorized histologically. Conclusion This study suggests that cytokines could be useful biomarkers of skin wound vitality and that the immunoassay method could be more sensitive than immunohistochemistry to identify wounds with a short survival time. Further research is underway to confirm these preliminary data.
- Published
- 2021
13. Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview
- Author
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Delaby, C, Teunissen, CE, Blennow, K, Alcolea, D, Arisi, I, Amar, EB, Beaume, A, Bedel, A, Bellomo, G, Bigot-Corbel, E, Bjerke, M, Blanc-Quintin, M-C, Boada, M, Bousiges, O, Chapman, MD, DeMarco, ML, D'Onofrio, M, Dumurgier, J, Dufour-Rainfray, D, Engelborghs, S, Esselmann, H, Fogli, A, Gabelle, A, Galloni, E, Gondolf, C, Grandhomme, F, Grau-Rivera, O, Hart, M, Ikeuchi, T, Jeromin, A, Kasuga, K, Keshavan, A, Khalil, M, Koertvelyessy, P, Kulczynska-Przybik, A, Laplanche, J-L, Lewczuk, P, Li, Q-X, Lleo, A, Malaplate, C, Marquie, M, Masters, CL, Mroczko, B, Nogueira, L, Orellana, A, Otto, M, Oudart, J-B, Paquet, C, Paoletti, FP, Parnetti, L, Perret-Liaudet, A, Peoc'h, K, Poesen, K, Puig-Pijoan, A, Quadrio, I, Quillard-Muraine, M, Rucheton, B, Schraen, S, Schott, JM, Shaw, LM, Suarez-Calvet, M, Tsolaki, M, Tumani, H, Udeh-Momoh, CT, Vaudran, L, Verbeek, MM, Verde, F, Vermunt, L, Vogelgsang, J, Wiltfang, J, Zetterberg, H, Lehmann, S, Delaby, C, Teunissen, CE, Blennow, K, Alcolea, D, Arisi, I, Amar, EB, Beaume, A, Bedel, A, Bellomo, G, Bigot-Corbel, E, Bjerke, M, Blanc-Quintin, M-C, Boada, M, Bousiges, O, Chapman, MD, DeMarco, ML, D'Onofrio, M, Dumurgier, J, Dufour-Rainfray, D, Engelborghs, S, Esselmann, H, Fogli, A, Gabelle, A, Galloni, E, Gondolf, C, Grandhomme, F, Grau-Rivera, O, Hart, M, Ikeuchi, T, Jeromin, A, Kasuga, K, Keshavan, A, Khalil, M, Koertvelyessy, P, Kulczynska-Przybik, A, Laplanche, J-L, Lewczuk, P, Li, Q-X, Lleo, A, Malaplate, C, Marquie, M, Masters, CL, Mroczko, B, Nogueira, L, Orellana, A, Otto, M, Oudart, J-B, Paquet, C, Paoletti, FP, Parnetti, L, Perret-Liaudet, A, Peoc'h, K, Poesen, K, Puig-Pijoan, A, Quadrio, I, Quillard-Muraine, M, Rucheton, B, Schraen, S, Schott, JM, Shaw, LM, Suarez-Calvet, M, Tsolaki, M, Tumani, H, Udeh-Momoh, CT, Vaudran, L, Verbeek, MM, Verde, F, Vermunt, L, Vogelgsang, J, Wiltfang, J, Zetterberg, H, and Lehmann, S
- Abstract
INTRODUCTION: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. METHODS: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. RESULTS: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. DISCUSSION: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.
- Published
- 2021
14. Detection of amyloid beta peptides in body fluids for the diagnosis of alzheimer's disease: Where do we stand?
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Veerabhadrappa, B, Delaby, C, Hirtz, C, Vialaret, J, Alcolea, D, Lleo, A, Fortea, J, Santosh, MS, Choubey, S, and Lehmann, S
- Subjects
saliva ,Amyloid peptides ,diagnosis ,blood ,Alzheimer disease ,cerebrospinal fluid - Abstract
Alzheimer's disease (AD) is an incurable neurodegenerative disease characterized by progressive decline of cognitive abilities. Amyloid beta peptides (A beta), Tau proteins and the phosphorylated form of the Tau protein, p-Tau, are the core pathological biomarkers of the disease, and their detection for the diagnosis of patients is progressively being implemented. However, to date, their quantification is mostly performed on cerebrospinal fluid (CSF), the collection of which requires an invasive lumbar puncture. Early diagnosis has been shown to be important for disease-modifying treatment, which is currently in development, to limit the progression of the disease. Nevertheless, the diagnosis is often delayed to the point where the disease has already progressed, and the tools currently available do not allow for a systematic follow-up of patients. Thus, the search for a molecular signature of AD in a body fluid such as blood or saliva that can be collected in a minimally invasive way offers hope. A number of methods have been developed for the quantification of core biomarkers, especially in easily accessible fluids such as the blood, that improve their accuracy, specificity and sensitivity. This review summarizes and compares these approaches, focusing in particular on their use for A beta detection, the earliest biomarker to be modified in the course of AD. The review also discusses biomarker quantification in CSF, blood and saliva and their clinical applications.
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- 2020
15. Metabolic modifications in the AIP mouse model treated by chronic haem administration: O03
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Yu, A., Delaby, C., Lyoumi, S., Benecke, A., Couchi, E., Rotter, B., Driss, F., Grandchamp, B., Beaumont, C., Deybach, J.-C., Puy, H., Gouya, L., and Schmitt, C.
- Published
- 2011
16. Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders
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Delaby, C., primary, Alcolea, D., additional, Carmona-Iragui, M., additional, Illán-Gala, I., additional, Morenas-Rodríguez, E., additional, Barroeta, I., additional, Altuna, M., additional, Estellés, T., additional, Santos-Santos, M., additional, Turon-Sans, J., additional, Muñoz, L., additional, Ribosa-Nogué, R., additional, Sala-Matavera, I., additional, Sánchez-Saudinos, B., additional, Subirana, A., additional, Videla, L., additional, Benejam, B., additional, Sirisi, S., additional, Lehmann, S., additional, Belbin, O., additional, Clarimon, J., additional, Blesa, R., additional, Pagonabarraga, J., additional, Rojas-Garcia, R., additional, Fortea, J., additional, and Lleó, A., additional
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- 2020
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17. Role of two nutritional hepatic markers (insulin-like growth factor 1 and transthyretin) in the clinical assessment and follow-up of acute intermittent porphyria patients
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Delaby, C., To-Figueras, J., Deybach, J. C., Casamitjana, R, Puy, H., and Herrero, C.
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- 2009
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18. Factorial correspondence analysis of fear-related behaviour traits in Japanese quail
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Mignon-Grasteau, S, Roussot, O, Delaby, C, Faure, J.M, Mills, A, Leterrier, C, Guéméné, D, Constantin, P, Mills, M, Lepape, G, and Beaumont, C
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- 2003
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19. Plasma and CSF biomarkers for the diagnosis of Alzheimer's disease in adults with Down syndrome: a cross-sectional study
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Fortea J., Carmona-Iragui M., Benejam B., Fernández S., Videla L., Barroeta I., Alcolea D., Pegueroles J., Muñoz L., Belbin O., de Leon M.J., Maceski A.M., Hirtz C., Clarimón J., Videla S., Delaby C., Lehmann S., Blesa R., and Lleó A.
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Adult ,Male ,Down syndrome ,Prodromal Symptoms ,tau Proteins ,prodromal symptom ,Comorbidity ,tau protein ,Article ,cerebrospinal fluid ,blood ,Alzheimer Disease ,Neurofilament Proteins ,middle aged ,cross-sectional study ,lumbar puncture ,Humans ,neurofilament protein ,controlled study ,human ,neurofilament protein L ,cerebrospinal fluid analysis ,Amyloid beta-Peptides ,biological marker ,major clinical study ,enzyme linked immunosorbent assay ,protein phosphorylation ,female ,Cross-Sectional Studies ,priority journal ,amyloid beta protein ,dementia - Abstract
Background: Diagnosis of Alzheimer's disease in Down syndrome is challenging because of the absence of validated diagnostic biomarkers. We investigated the diagnostic performance of plasma and CSF biomarkers in this population. Methods: We did a cross-sectional study of adults aged 18 years and older with Down syndrome enrolled in a population-based health plan in Catalonia, Spain. Every person with Down syndrome assessed in the health plan was eligible to enter the Down Alzheimer Barcelona Neuroimaging Initiative, and those with a plasma or CSF sample available were included in this study. Participants underwent neurological and neuropsychological examination and blood sampling, and a subset underwent a lumbar puncture. Adults with Down syndrome were classified into asymptomatic, prodromal Alzheimer's disease, or Alzheimer's disease dementia groups by investigators masked to biomarker data. Non-trisomic controls were a convenience sample of young (23–58 years) healthy people from the Sant Pau Initiative on Neurodegeneration. Amyloid-ß (Aß) 1–40 , Aß 1–42 , total tau (t-tau), 181-phosphorylated tau (p-tau; only in CSF), and neurofilament light protein (NfL) concentrations were measured in plasma with a single molecule array assay and in CSF with ELISA. Plasma and CSF biomarker concentrations were compared between controls and the Down syndrome clinical groups. Diagnostic performance was assessed with receiver operating characteristic curve analyses between asymptomatic participants and those with prodromal Alzheimer's disease and between asymptomatic participants and those with Alzheimer's disease dementia. Findings: Between Feb 1, 2013, and Nov 30, 2017, we collected plasma from 282 participants with Down syndrome (194 asymptomatic, 39 prodromal Alzheimer's disease, 49 Alzheimer's disease dementia) and 67 controls; CSF data were available from 94 participants (54, 18, and 22, respectively) and all 67 controls. The diagnostic performance of plasma biomarkers was poor (area under the curve [AUC] between 0·53 [95% CI 0·44–0·62] and 0·74 [0·66–0·82]) except for plasma NfL concentrations, which had an AUC of 0·88 (0·82–0·93) for the differentiation of the asymptomatic group versus the prodromal Alzheimer's disease group and 0·95 (0·92–0·98) for the asymptomatic group versus the Alzheimer's disease dementia group. In CSF, except for Aß 1–40 concentrations (AUC 0·60, 95% CI 0·45–0·75), all biomarkers had a good performance in the asymptomatic versus prodromal Alzheimer's disease comparison: AUC 0·92 (95% CI 0·85–0·99) for Aß 1–42 , 0·81 (0·69–0·94) for t-tau, 0·80 (0·67–0·93) for p-tau, and 0·88 (0·79–0·96) for NfL. Performance of the CSF biomarkers was optimal in the asymptomatic versus Alzheimer's disease dementia comparison (AUC =0·90 for all except Aß 1–40 [0·59, 0·45–0·72]). Only NfL concentrations showed a strong correlation between plasma and CSF biomarker concentrations in participants with Down syndrome (rho=0·80; p
- Published
- 2018
20. Iron deficiency during first-line chemotherapy in metastatic cancers: a prospective epidemiological study
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Saint, Angélique, primary, Viotti, J., additional, Borchiellini, D., additional, Hoch, B., additional, Raimondi, V., additional, Hebert, C., additional, Largillier, R., additional, Evesque, L., additional, Follana, P., additional, Ferrero, J. M., additional, Delaby, C., additional, Schiappa, R., additional, Chamorey, E., additional, and Barriere, J., additional
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- 2019
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21. Hepcidine ou ferritine : quel biomarqueur pour le Syndrome des jambes sans repos ?
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Chenini, S., primary, Jaussent, I., additional, Delaby, C., additional, Guirand, L., additional, Scholz, S., additional, Lopez, R., additional, Rassu, A.-L., additional, Hirtz, C., additional, Lehmann, S., additional, and Dauvilliers, Y., additional
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- 2019
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22. Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model
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Millot, S., Delaby, C., Moulouel, B., Lefebvre, T., Pilard, N., Ducrot, N., Ged, C., Lettéron, P., DE FRANCESCHI, Lucia, Deybach, J., Beaumont, C., Gouya, L., De Verneuil, H., Lyoumi, S., Puy, H., and Karim, Z.
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hemolytic anemia, hepcidin, iron overload ,hepcidin ,iron overload ,hemolytic anemia - Published
- 2017
23. Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver
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Schmitt, C., primary, Lenglet, H., additional, Yu, A., additional, Delaby, C., additional, Benecke, A., additional, Lefebvre, T., additional, Letteron, P., additional, Paradis, V., additional, Wahlin, S., additional, Sandberg, S., additional, Harper, P., additional, Sardh, E., additional, Sandvik, A. K., additional, Hov, J. R., additional, Aarsand, A. K., additional, Chiche, L., additional, Bazille, C., additional, Scoazec, J.‐Y., additional, To-Figueras, J., additional, Carrascal, M., additional, Abian, J., additional, Mirmiran, A., additional, Karim, Z., additional, Deybach, J.‐C., additional, Puy, H., additional, Peoc'h, K., additional, Manceau, H., additional, and Gouya, L., additional
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- 2018
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24. L’hepcidine : un nouveau biomarqueur de la maladie d’Ekbom–Willis ?
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Chenini, S., primary, Vialaret, J., additional, Delaby, C., additional, Guiraud, L., additional, Gabelle, A., additional, Lopez, R., additional, Hirtz, C., additional, Jaussent, I., additional, Lehmann, S., additional, and Dauvilliers, Y., additional
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- 2018
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25. AFC de différents caractères de comportement liés au stress chez la caille
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Delaby, C., Université Pierre et Marie Curie - Paris 6 (UPMC), Inconnu, FRA., and Inconnu Inconnu
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MULTIFACTORIAL ANALYSIS ,STRESS ,[SDV]Life Sciences [q-bio] ,BEHAVIOUR ,JAPANESE QUAILS - Abstract
Diplôme : Rapport de stage
- Published
- 2001
26. L'hepcidine et le métabolisme du fer
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Delaby, C., primary, Deybach, J.-C., additional, and Beaumont, C., additional
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- 2007
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27. Development of a proteomic approach to characterize murine biological markers of acute intermittent porphyria
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Delaby, C., Abian, J., To-Figueras, J., Martin-Schmitt, C., Gouya, L., HERVE PUY, Beaumont, C., and Deybach, J. -C
28. Clinical value of plasma ALZpath pTau217 immunoassay for assessing mild cognitive impairment.
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Lehmann S, Schraen-Maschke S, Vidal JS, Delaby C, Buee L, Blanc F, Paquet C, Allinquant B, Bombois S, Gabelle A, and Hanon O
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- Humans, Male, Female, Aged, Immunoassay, Aged, 80 and over, Prospective Studies, Peptide Fragments blood, Disease Progression, Middle Aged, Cognitive Dysfunction blood, Cognitive Dysfunction diagnosis, tau Proteins blood, Biomarkers blood, Amyloid beta-Peptides blood, Alzheimer Disease blood, Alzheimer Disease diagnosis
- Abstract
Background: Among plasma biomarkers for Alzheimer's disease (AD), pTau181 and pTau217 are the most promising. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors., Method: pTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well-characterised prospective multicentre BALTAZAR (Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk) cohort of participants with mild cognitive impairment (MCI)., Results: Among participants with MCI, 55% were Aβ+ and 29% developed dementia due to AD. pTau181 and pTau217 were higher in the Aβ+ population with fold change of 1.5 and 2.7, respectively. MCI that converted to AD also had higher levels than non-converters, with HRs of 1.38 (1.26 to 1.51) for pTau181 compared with 8.22 (5.45 to 12.39) for pTau217. The area under the curve for predicting Aβ+ was 0.783 (95% CI 0.721 to 0.836; cut-point 2.75 pg/mL) for pTau181 and 0.914 (95% CI 0.868 to 0.948; cut-point 0.44 pg/mL) for pTau217. The high predictive power of pTau217 was not improved by adding age, sex and apolipoprotein E ε4 (APOEε4) status, in a logistic model. Age, APOEε4 and renal dysfunction were associated with pTau levels, but the clinical performance of pTau217 was only marginally altered by these factors. Using a two cut-point approach, a 95% positive predictive value for Aβ+ corresponded to pTau217 >0.8 pg/mL and a 95% negative predictive value at <0.23 pg/mL. At these two cut-points, the percentages of MCI conversion were 56.8% and 9.7%, respectively, while the annual rates of decline in Mini-Mental State Examination were -2.32 versus -0.65., Conclusions: Plasma pTau217 and pTau181 both correlate with AD, but the fold change in pTau217 makes it better to diagnose cerebral amyloidosis, and predict cognitive decline and conversion to AD dementia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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29. Clarifying the association of CSF Aβ, tau, BACE1, and neurogranin with AT(N) stages in Alzheimer disease.
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Lehmann S, Schraen-Maschke S, Buée L, Vidal JS, Delaby C, Hirtz C, Blanc F, Paquet C, Allinquant B, Bombois S, Gabelle A, and Hanon O
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- Humans, Aged, Male, Female, Middle Aged, Aged, 80 and over, Alzheimer Disease cerebrospinal fluid, tau Proteins cerebrospinal fluid, Amyloid Precursor Protein Secretases cerebrospinal fluid, Amyloid Precursor Protein Secretases metabolism, Amyloid beta-Peptides cerebrospinal fluid, Neurogranin cerebrospinal fluid, Aspartic Acid Endopeptidases cerebrospinal fluid, Biomarkers cerebrospinal fluid
- Abstract
Background: Current AT(N) stratification for Alzheimer's disease (AD) accounts for complex combinations of amyloid (A), tau proteinopathy (T) and neurodegeneration (N) signatures. Understanding the transition between these different stages is a major challenge, especially in view of the recent development of disease modifying therapy., Methods: This is an observational study, CSF levels of Tau, pTau181, pTau217, Aβ38/40/42, sAPPα/β, BACE1 and neurogranin were measured in the BALTAZAR cohort of cognitively impaired patients and in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Biomarkers levels were related to the AT(N) framework. (A) and (T) were defined in BALTAZAR with CSF Aβ42/40 ratio and pTau217 respectively, and in ADNI with amyloid and tau PET. (N) was defined using total CSF tau in both cohorts., Results: As expected, CSF Aβ42 decreased progressively with the AD continuum going from the A-T-N- to the A + T + N + profile. On the other hand, Tau and pTau181 increased progressively with the disease. The final transition from A + T + N- to A + T + N + led to a sharp increase in Aβ38, Aβ42 and sAPP levels. Synaptic CSF biomarkers BACE1 and neurogranin, were lowest in the initial A + T-N- stage and increased with T + and N + . CSF pTau181 and total tau were closely related in both cohorts., Conclusions: The early transition to an A + phenotype (A + T-N-) primarily impacts synaptic function. The appearance of T + and then N + is associated with a significant and progressive increase in pathological Alzheimer's disease biomarkers. Our main finding is that CSF pTau181 is an indicator of N + rather than T + , and that N + is associated with elevated levels of BACE1 protein and beta-amyloid peptides. This increase may potentially fuel the amyloid cascade in a positive feedback loop. Overall, our data provide further insights into understanding the interconnected pathological processes of amyloid, tau, and neurodegeneration underlying Alzheimer's disease., (© 2024. The Author(s).)
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- 2024
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30. Challenges in the practical implementation of blood biomarkers for Alzheimer's disease.
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Schöll M, Verberk IMW, Del Campo M, Delaby C, Therriault J, Chong JR, Palmqvist S, and Alcolea D
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- Humans, Alzheimer Disease blood, Alzheimer Disease diagnosis, Biomarkers blood
- Abstract
Blood biomarkers have emerged as accessible, cost-effective, and highly promising tools for advancing the diagnostics of Alzheimer's disease. However, transitioning from cerebrospinal fluid biomarkers to blood biomarkers-eg, to verify amyloid β pathology-requires careful consideration. This Series paper highlights the main challenges in the implementation of blood biomarkers for Alzheimer's disease in different possible contexts of use. Despite the robustness of measuring blood biomarker concentrations, the widespread adoption of blood biomarkers requires rigorous standardisation efforts to address inherent challenges in diverse contexts of use. The challenges include understanding the effect of pre-analytical and analytical conditions, potential confounding factors, and comorbidities that could influence outcomes of blood biomarkers and their use in diverse populations. Additionally, distinct scenarios present their own specific challenges. In memory clinics, the successful integration of blood biomarkers in diagnostic tests will require well-established diagnostic accuracy and comprehensive assessments of the effect of blood biomarkers on the diagnostic confidence and patient management of clinicians. In primary care settings, and even more when implemented in population-based screening programmes for which no experience with any biomarkers for Alzheimer's disease currently exists, the implementation of blood biomarkers will be challenged by the need for education of primary care clinical staff and clear guidelines. However, despite the challenges, blood biomarkers hold great promise for substantially enhancing the diagnostic accuracy and effectively streamlining referral processes, leading to earlier diagnosis and access to treatments. The ongoing efforts that are shaping the integration of blood biomarkers across diverse clinical settings pave the way towards precision medicine in Alzheimer's disease., Competing Interests: Declaration of interests MS has served on the advisory boards for Roche and Novo Nordisk; received speaker honoraria from Bioarctic, Novo Nordisk, and Roche; and receives research support (to the institution) from Alzpath, Bioarctic, Novo Nordisk, and Roche (outside the scope of the submitted work). MS is a co-founder of Centile Bioscience, which develops imaging-based diagnostic support solutions and serves as an Associate Editor of Alzheimer’s Research & Therapy. IMWV declares honoraria from Quanterix. MdC declares contracts or grants from the Ministerio Español de Ciencia e innovación (PROYECTOS I+D+I – 2020 – Retos de investigación), Europe Research 2020 dynamisation actions:payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novo Nordisk and Springer Healthcare; participation as an associate editor at Alzheimer´s Research & Therapy; on the review board of Galen and Hilary Weston Foundation, and the review board of Alzheimer’s Research UK; and travel support from the Alzheimer’s Association. JT declares consulting fees from the Neurotorium Educational Platform. SP declares support from Avid, ki:elements, and Alzheimer's Drug Discovery Foundation; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bioarctic, Biogen, Eisai, Lilly, and Roche. DA declares contracts or grants from the Institute of Health Carlos III and the Department of Health Generalitat de Catalunya; participation in advisory boards of Fujirebio-Europe, Roche Diagnostics, Grifols SA, and Lilly; and speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia, Krka Farmaceutica, Zambon, and Esteve Pharmaceuticals. DA declares a filed patent application (WO2019175379 A1 Markers of synaptopathy in neurodegenerative disease). CD and JRC declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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31. Association of caffeine consumption with cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease: A BALTAZAR cohort study.
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Blum D, Cailliau E, Béhal H, Vidal JS, Delaby C, Buée L, Allinquant B, Gabelle A, Bombois S, Lehmann S, Schraen-Maschke S, and Hanon O
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- Humans, Male, Female, Aged, Cohort Studies, Middle Aged, Alzheimer Disease cerebrospinal fluid, Cognitive Dysfunction cerebrospinal fluid, Biomarkers cerebrospinal fluid, Caffeine cerebrospinal fluid, Amyloid beta-Peptides cerebrospinal fluid, tau Proteins cerebrospinal fluid, Peptide Fragments cerebrospinal fluid
- Abstract
Introduction: We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients., Methods: MCI (N = 147) and AD (N = 116) patients of the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) cohort reported their caffeine intake at inclusion using a dedicated survey. Associations of caffeine consumption with memory impairments and CSF biomarkers (tau, p-tau181, amyloid beta 1-42 [Aβ
1-42 ], Aβ1-40 ) were analyzed using logistic and analysis of covariance models., Results: Adjusted on Apolipoprotein E (APOE ε4), age, sex, education level, and tobacco, lower caffeine consumption was associated with higher risk to be amnestic (OR: 2.49 [95% CI: 1.13 to 5.46]; p = 0.023) and lower CSF Aβ1-42 (p = 0.047), Aβ1-42 /Aβ1-40 (p = 0.040), and Aβ1-42 /p-tau181 (p = 0.020) in the whole cohort., Discussion: Data support the beneficial effect of caffeine consumption to memory impairments and CSF amyloid markers in MCI and AD patients., Highlights: We studied the impact of caffeine consumption in the BALTAZAR cohort. Low caffeine intake is associated with higher risk of being amnestic in MCI/AD patients. Caffeine intake is associated with CSF biomarkers in AD patients., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)- Published
- 2024
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32. Interaction between females and males grapevine moth Lobesia botrana modifies further mating preference.
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Lorrain-Soligon L, Muller K, Delaby C, Thiéry D, and Moreau J
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- Animals, Male, Female, Sexual Behavior, Animal, Spermatogonia physiology, Lobesia botrana, Moths physiology, Sex Attractants pharmacology, Mating Preference, Animal
- Abstract
During reproduction, females may boost their fitness by being selective based on direct material benefits provided by the males, such as nuptial gifts. In Lepidoptera, male provides a spermatophore containing nutrients. However, virgin males produce a bigger spermatophore, containing spermatozoa and nutrients, allowing higher female fertility. Lepidoptera females that could detect the sexual status of males may thus prefer a male without previous mating experience (i.e. a virgin male). This mate selection could be achieved by the use of chemical indices, such as sexual pheromones and cuticular compounds, known to be possibly exchanged during reproduction, and which can be indicators of a previous mating experience and known to be possibly sources of information exchanged. In this study, we experimentally presented Lobesia botrana virgin males with females in order for them to be exposed to females' natural sexual pheromones or cuticular compounds. 12 or 48 h after the exposure of males to either females' sexual pheromones or cuticular compounds, these males were confronted to naïve females, which have a choice between them or a virgin non-exposed males. We highlighted that, despite producing a spermatophore of similar volume, all exposed virgin males were less likely to mate with females 12 h after exposure, while after 48 h of exposure this is only the case for virgin males exposed to sexual pheromones. L. botrana females may thus discriminate male sexual experience based on chemical cues (either from cues transferred directly from females to males, or from changes in the cuticular or pheromone males' profile) indicating past mating experiences. Mating duration was longer for males exposed to sexual pheromones after 12 h only, and for males exposed to cuticular compounds after 48 h only. Pheromones signal might be more persistent over time and seems to more easily gather information for males. The physiological reasoning behind this result still needs to be investigated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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33. [On the road to biological blood diagnosis of Alzheimer's disease?]
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Delaby C and Lehmann S
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- Humans, tau Proteins blood, tau Proteins cerebrospinal fluid, Amyloid beta-Peptides blood, Amyloid beta-Peptides cerebrospinal fluid, Diagnosis, Differential, Alzheimer Disease diagnosis, Alzheimer Disease blood, Biomarkers blood
- Abstract
The growing number of people suffering from Alzheimer's disease (AD) represents a major public health problem. The diagnosis of AD is multidisciplinary and involves the use of amyloid and tau biomarkers measured in cerebrospinal fluid. Recent advances in analytical techniques now allow us to measure these biomarkers in blood. Blood biomarkers offer particularly promising potential for early, minimally invasive detection of AD, as well as for differential diagnosis of dementia and patient follow-up. The aim of this review is to provide an overview of current and candidate blood biomarkers for AD, their informative value, and their potential to be integrated into clinical practice in the near future., (© 2024 médecine/sciences – Inserm.)
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- 2024
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34. Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer's Disease Continuum.
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Lehmann S, Schraen-Maschke S, Vidal JS, Blanc F, Paquet C, Allinquant B, Bombois S, Gabelle A, Delaby C, and Hanon O
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- Humans, Prospective Studies, Intermediate Filaments, Neurofilament Proteins, Biomarkers, Amyloid beta-Peptides, Disease Progression, tau Proteins, Alzheimer Disease diagnosis, Cognitive Dysfunction diagnosis
- Abstract
Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer's disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did not have a clinically determined diagnosis of dementia by the end of the three-year study. Additionally, we explored the connection between baseline plasma concentration of NfL and AD dementia patients, considering their demographics, clinical features, and cognitive profiles. A total of 350 participants from the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) multicenter prospective study were investigated: 161 AD dementia participants and 189 MCI participants (of which 141 had amnestic MCI and 48 non-amnestic MCI). Plasma biomarkers were measured at baseline and the progression of clinical and cognitive profiles was followed over the three years of follow-up. Baseline plasma NfL concentration increased across the Alzheimer's disease continuum with a mean NfL value of 17.1 ng/mL [SD = 6.1] in non-amnestic MCI, 20.7 ng/mL [SD = 12.0] in amnestic MCI, and 23.1 ng/mL [SD = 22.7] in AD dementia patients. Plasma NfL concentration correlated with age, body mass index (BMI), and global cognitive performance and decline, as measured by the Mini-Mental State Examination (MMSE). MMSE scores decreased in parallel with increasing plasma NfL concentration, independently of age and BMI. However, NfL concentration did not predict MCI participants' conversion to dementia within three years. Discussion: Baseline plasma NfL concentration is associated with cognitive status along the AD continuum, suggesting its usefulness as a potential informative biomarker for cognitive decline follow-up in patients.
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- 2023
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35. Head-to-Head Comparison of Two Plasma Phospho-tau Assays in Predicting Conversion of Mild Cognitive Impairment to Dementia.
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Lehmann S, Schraen-Maschke S, Vidal JS, Delaby C, Blanc F, Paquet C, Allinquant B, Bombois S, Gabelle A, and Hanon O
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- Humans, Prospective Studies, Plasma, Adiponectin, Alzheimer Disease, Cognitive Dysfunction diagnosis
- Abstract
Background: Among blood biomarkers, phospho-tau181 (pTau181) is one of the most efficient in detecting Alzheimer disease across its continuum. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors., Methods: Here we tested the Lumipulse assay for plasma pTau181 in mild cognitive impairment (MCI) participants from the Baltazar prospective cohort. We compared the performance of this assay to the corresponding Simoa assay for the prediction of conversion to dementia. We also evaluated the association with various routine blood parameters indicative of comorbidities., Results: Lumipulse and Simoa gave similar results overall, with hazard ratios for conversion to dementia of 3.48 (95% CI, 2.23-5.45) and 3.70 (95%CI, 2.39-5.87), respectively. However, the 2 tests differ somewhat in terms of the patients identified, suggesting that their use may be complementary. When combined with age, sex, and apolipoprotein E (APOE)ε4 status, areas under the curves for conversion detection were 0.736 (95% CI, 0.682-0.791) for Lumipulse and 0.733 (95% CI, 0.679-0.788) for Simoa. Plasma pTau181 was independently associated with renal dysfunction (assessed by creatinine and glomerular filtration) for both assays. Cardiovascular factors (adiponectin and cholesterol), nutritional, and inflammatory markers (total protein content, C-reactive protein) also impacted plasma pTau181 concentration, although more so with the Simoa than with the Lumipulse assay., Conclusions: Plasma pTau181 measured using the fully automated Lumipulse assay performs as well as the Simoa assay for detecting conversion to dementia of MCI patients within 3 years and Lumipulse is less affected by comorbidities. This study suggests a pathway to routine noninvasive in vitro diagnosis-approved testing to contribute to the management of Alzheimer disease., Clinicaltrials.gov Registration Number: NCT01315639., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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36. Serum neurofilament light chain cut-off definition for clinical diagnosis and prognosis of amyotrophic lateral sclerosis.
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Brousse M, Delaby C, De La Cruz E, Kuhle J, Benkert P, Mondesert E, Ginestet N, Hirtz C, Camu W, Lehmann S, and Esselin F
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- Humans, Intermediate Filaments, Prognosis, Biomarkers, Neurofilament Proteins, Body Mass Index, Amyotrophic Lateral Sclerosis diagnosis
- Abstract
Background: The neurofilament light chain (NfL) assay is gradually becoming an essential diagnostic tool for the diagnosis of many neurological diseases including amyotrophic lateral sclerosis (ALS). Different methods for the determination of this biomarker in serum have been developed in recent years., Methods: We measured blood NfL in 429 patients referred to the tertiary ALS center of Montpellier, France using two different ultrasensitive methods (Ella™ and Simoa™) and we compared the clinical performances of these two approaches. We also converted NfL values into age and body mass index-adjusted Z-scores to assess cut-off values of this biomarker in this clinical context., Results: We show comparable diagnostic and prognostic performance of Ella™ and Simoa™ technologies in ALS, with specificities and sensitivities exceeding 80% for both. We propose cut-off values for serum NfL in this clinical context, thus enabling the routine clinical use of this biomarker., Conclusion: The use of NfL in routine clinical practice will help predict survival and improve diagnostic accuracy by distinguishing ALS from other neurological diseases and motor neuron disease mimics., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
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- 2023
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37. Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function.
- Author
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Lehmann S, Schraen-Maschke S, Vidal JS, Delaby C, Blanc F, Paquet C, Allinquant B, Bombois S, Gabelle A, and Hanon O
- Subjects
- Humans, tau Proteins, Amyloid beta-Peptides, Prospective Studies, Biomarkers, Kidney physiology, Alzheimer Disease diagnosis, Cognitive Dysfunction diagnosis
- Abstract
Objectives: Plasma P-tau181 is an increasingly established diagnostic marker for Alzheimer's disease (AD). Further validation in prospective cohorts is still needed, as well as the study of confounding factors that could influence its blood level., Methods: This study is ancillary to the prospective multicentre Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk cohort that enrolled participants with mild cognitive impairment (MCI) who were examined for conversion to dementia for up to 3 years. Plasma Ptau-181 was measured using the ultrasensitive Quanterix HD-X assay., Results: Among 476 MCI participants, 67% were amyloid positive (Aβ+) at baseline and 30% developed dementia. Plasma P-tau181 was higher in the Aβ+ population (3.9 (SD 1.4) vs 2.6 (SD 1.4) pg/mL) and in MCI that converted to dementia (3.8 (SD 1.5) vs 2.9 (SD 1.4) pg/mL). The addition of plasma P-tau181 to a logistic regression model combining age, sex, APOEε4 status and Mini Mental State Examination improved predictive performance (areas under the curve 0.691-0.744 for conversion and 0.786-0.849 for Aβ+). The Kaplan-Meier curve of conversion to dementia, according to the tertiles of plasma P-tau181, revealed a significant predictive value (Log rank p<0.0001) with an HR of 3.8 (95% CI 2.5 to 5.8). In addition, patients with plasma P-Tau(181) ≤2.32 pg/mL had a conversion rate of less than 20% over a 3-year period. Using a linear regression approach, chronic kidney disease, creatinine and estimated glomerular filtration rate were independently associated with plasma P-tau181 concentrations., Conclusions: Plasma P-tau181 effectively detects Aβ+ status and conversion to dementia, confirming the value of this blood biomarker for the management of AD. However, renal function significantly modifies its levels and may thus induce diagnostic errors if not taken into account., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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38. β-Synuclein as a candidate blood biomarker for synaptic degeneration in Alzheimer's disease.
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Mohaupt P, Pons ML, Vialaret J, Delaby C, Hirtz C, and Lehmann S
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- Humans, Biomarkers, beta-Synuclein, Alzheimer Disease diagnosis
- Abstract
Synaptic degeneration is an early event closely associated with the course of Alzheimer's disease (AD). The identification of synaptic blood biomarkers is, therefore, of great interest and clinical relevance. The levels of most synaptic proteins are increased in the cerebrospinal fluid (CSF) of patients with AD, but their detection in blood is hitherto either unavailable or not very informative. This paradigm is related to their low concentration, their peripheral origin, or the presence of highly abundant blood proteins that hinder detection. In recent years, significant progress has been made in detecting the presynaptic protein β-synuclein. This mini-review summarizes the results that highlight the role of β-synuclein as a candidate blood marker for synaptic degeneration in AD., (© 2022. The Author(s).)
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- 2022
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39. The alternative proteome in neurobiology.
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Mohaupt P, Roucou X, Delaby C, Vialaret J, Lehmann S, and Hirtz C
- Abstract
Translation involves the biosynthesis of a protein sequence following the decoding of the genetic information embedded in a messenger RNA (mRNA). Typically, the eukaryotic mRNA was considered to be inherently monocistronic, but this paradigm is not in agreement with the translational landscape of cells, tissues, and organs. Recent ribosome sequencing (Ribo-seq) and proteomics studies show that, in addition to currently annotated reference proteins (RefProt), other proteins termed alternative proteins (AltProts), and microproteins are encoded in regions of mRNAs thought to be untranslated or in transcripts annotated as non-coding. This experimental evidence expands the repertoire of functional proteins within a cell and potentially provides important information on biological processes. This review explores the hitherto overlooked alternative proteome in neurobiology and considers the role of AltProts in pathological and healthy neuromolecular processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mohaupt, Roucou, Delaby, Vialaret, Lehmann and Hirtz.)
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- 2022
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40. Neurofilaments contribution in clinic: state of the art.
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Delaby C, Bousiges O, Bouvier D, Fillée C, Fourier A, Mondésert E, Nezry N, Omar S, Quadrio I, Rucheton B, Schraen-Maschke S, van Pesch V, Vicca S, Lehmann S, and Bedel A
- Abstract
Neurological biomarkers are particularly valuable to clinicians as they can be used for diagnosis, prognosis, or response to treatment. This field of neurology has evolved considerably in recent years with the improvement of analytical methods, allowing the detection of biomarkers not only in cerebrospinal fluid (CSF) but also in less invasive fluids like blood. These advances greatly facilitate the repeated quantification of biomarkers, including at asymptomatic stages of the disease. Among the various informative biomarkers of neurological disorders, neurofilaments (NfL) have proven to be of particular interest in many contexts, such as neurodegenerative diseases, traumatic brain injury, multiple sclerosis, stroke, and cancer. Here we discuss these different pathologies and the potential value of NfL assay in the management of these patients, both for diagnosis and prognosis. We also describe the added value of NfL compared to other biomarkers currently used to monitor the diseases described in this review., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Delaby, Bousiges, Bouvier, Fillée, Fourier, Mondésert, Nezry, Omar, Quadrio, Rucheton, Schraen-Maschke, van Pesch, Vicca, Lehmann and Bedel.)
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- 2022
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41. Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.
- Author
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Delaby C, Teunissen CE, Blennow K, Alcolea D, Arisi I, Amar EB, Beaume A, Bedel A, Bellomo G, Bigot-Corbel E, Bjerke M, Blanc-Quintin MC, Boada M, Bousiges O, Chapman MD, DeMarco ML, D'Onofrio M, Dumurgier J, Dufour-Rainfray D, Engelborghs S, Esselmann H, Fogli A, Gabelle A, Galloni E, Gondolf C, Grandhomme F, Grau-Rivera O, Hart M, Ikeuchi T, Jeromin A, Kasuga K, Keshavan A, Khalil M, Körtvelyessy P, Kulczynska-Przybik A, Laplanche JL, Lewczuk P, Li QX, Lleó A, Malaplate C, Marquié M, Masters CL, Mroczko B, Nogueira L, Orellana A, Otto M, Oudart JB, Paquet C, Paoletti FP, Parnetti L, Perret-Liaudet A, Peoc'h K, Poesen K, Puig-Pijoan A, Quadrio I, Quillard-Muraine M, Rucheton B, Schraen S, Schott JM, Shaw LM, Suárez-Calvet M, Tsolaki M, Tumani H, Udeh-Momoh CT, Vaudran L, Verbeek MM, Verde F, Vermunt L, Vogelgsang J, Wiltfang J, Zetterberg H, and Lehmann S
- Subjects
- Humans, Biomarkers cerebrospinal fluid, Amyloid beta-Peptides cerebrospinal fluid, tau Proteins cerebrospinal fluid, Peptide Fragments cerebrospinal fluid, Alzheimer Disease diagnosis, Alzheimer Disease cerebrospinal fluid
- Abstract
Introduction: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests., Methods: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients., Results: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis., Discussion: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2022
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42. Neurofilaments: a key new biomarker for clinicians. Part 1: Importance of neurofilaments in the management of neurodegenerative diseases
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Delaby C, Bousiges O, Bouvier D, Fillée C, Fourier A, Mondésert É, Nezry N, Omar S, Quadrio I, Rucheton B, Schraen-Maschke S, van Pesch V, Vicca S, Lehmann S, and Bedel A
- Subjects
- Humans, Biomarkers, Intermediate Filaments, Neurodegenerative Diseases diagnosis, Neurodegenerative Diseases therapy
- Abstract
Neurological biomarkers are of great use for clinicians, as they can be used for numerous purposes: guiding clinical diagnosis, estimating prognosis, assessing disease stage and monitoring progression or response to treatment. This field of neurology has evolved considerably in recent years due to analytical improvements in assay methods, now allowing the detection of biomarkers not only in cerebrospinal fluid (CSF) but also in blood. This progress greatly facilitates the repeated quantification of biomarkers, the collection of blood being much less invasive than that of CSF. Among the various informative biomarkers of neurological disorders, neurofilaments light chains (NfL) have proven to be particularly attractive in many contexts, in particular for the diagnosis and prognosis of neurodegenerative diseases (which this review will present), but also in other contexts of neurological disorders (which will be detailed in part 2). We further address the added value of NfL compared to other biomarkers commonly used to monitor the diseases described in this review.
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- 2022
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43. Neurofilaments: a key new biomarker for clinicians. Part 2: Neurofilaments, an asset beyond neurodegenerative diseases
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Delaby C, Bousiges O, Bouvier D, Fillée C, Fourier A, Mondésert É, Nezry N, Omar S, Quadrio I, Rucheton B, Schraen-Maschke S, van Pesch V, Vicca S, Lehmann S, and Bedel A
- Subjects
- Humans, Intermediate Filaments, Biomarkers, Biological Assay, Neurodegenerative Diseases diagnosis, Multiple Sclerosis diagnosis
- Abstract
Neurofilaments (Nf) are proteins selectively expressed in the cytoskeleton of neurons, and their increase is a marker of neuronal damage. The potential utility of neurofilament light chain (NfL) has recently increased considerably, well beyond neurodegenerative diseases, due to analytical advances that allow measurement of their concentrations (even low ones) in cerebrospinal fluid and blood. This article completes the first part, in which we presented the interest of NfL in the context of neurodegenerative diseases. Here we focus our review on other clinical contexts of neurological injury (such as traumatic brain injury, multiple sclerosis, stroke, and cancer) and present the potential value of NfL assay in the management of these patients, for both diagnosis and prognosis. We also discuss the added value of the NfL assay compared to other biomarkers commonly used in the described clinical situations.
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- 2022
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44. Blood amyloid and tau biomarkers as predictors of cerebrospinal fluid profiles.
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Delaby C, Alcolea D, Hirtz C, Vialaret J, Kindermans J, Morichon L, Fortea J, Belbin O, Gabelle A, Blennow K, Zetterberg H, Lleó A, and Lehmann S
- Subjects
- Biomarkers cerebrospinal fluid, Humans, Peptide Fragments cerebrospinal fluid, Sensitivity and Specificity, tau Proteins metabolism, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease diagnosis, Amyloid beta-Peptides cerebrospinal fluid
- Abstract
Introduction: Blood biomarkers represent a major advance for improving the management, diagnosis, and monitoring of Alzheimer's disease (AD). However, their context of use in relation to routine cerebrospinal fluid (CSF) analysis for the quantification of amyloid peptides and tau proteins remains to be determined., Methods: We studied in two independent cohorts, the performance of blood biomarkers in detecting "nonpathological" (A-/T-/N-), amyloid (A+) or neurodegenerative (T+ /N+) CSF profiles., Results: Plasma Aβ
1-42 /Aβ1-40 ratio and phosphorylated tau (p-tau(181)) were independent and complementary predictors of the different CSF profile and in particular of the nonpathological (A-/T-/N-) profile with a sensitivity and specificity close to 85%. These performances and the corresponding biomarker thresholds were significantly different from those related to AD detection., Conclusion: The use of blood biomarkers to identify patients who may benefit from secondary CSF testing represents an attractive stratification strategy in the clinical management of patients visiting memory clinics. This could reduce the need for lumbar puncture and foreshadow the use of blood testing on larger populations., (© 2022. The Author(s).)- Published
- 2022
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45. The Aβ1-42/Aβ1-40 ratio in CSF is more strongly associated to tau markers and clinical progression than Aβ1-42 alone.
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Delaby C, Estellés T, Zhu N, Arranz J, Barroeta I, Carmona-Iragui M, Illán-Gala I, Santos-Santos MÁ, Altuna M, Sala I, Sánchez-Saudinós MB, Videla L, Valldeneu S, Subirana A, Tondo M, Blanco-Vaca F, Lehmann S, Belbin O, Blesa R, Fortea J, Lleó A, and Alcolea D
- Subjects
- Biomarkers cerebrospinal fluid, Humans, Peptide Fragments cerebrospinal fluid, Alzheimer Disease cerebrospinal fluid, Amyloid beta-Peptides cerebrospinal fluid, tau Proteins cerebrospinal fluid
- Abstract
Background: Cerebrospinal fluid (CSF) Aβ1-42 levels and the Aβ1-42/Aβ1-40 ratio are markers of amyloid pathology, but previous studies suggest that their levels might be influenced by additional pathophysiological processes., Aims: To compare Aβ1-42 and the Aβ1-42/Aβ1-40 ratio in CSF in different neurodegenerative disorders and study their association with other biomarkers (tTau, pTau181, and NfL) and with cognitive and functional progression., Methods: We included all participants from the Sant Pau Initiative on Neurodegeneration (SPIN) with CSF Aβ1-42 and Aβ1-42/Aβ1-40. Participants had diagnoses of Alzheimer's disease (AD), dementia with Lewy bodies, frontotemporal lobar degeneration-related syndromes, non-neurodegenerative conditions, or were cognitively normal. We classified participants as "positive" or "negative" according to each marker. We compared CSF levels of tTau, pTau181, and NfL between concordant and discordant groups through ANCOVA and assessed differences in cognitive (MMSE, FCSRT) and functional (GDS, CDR-SOB) progression using Cox regression and linear-mixed models., Results: In the 1791 participants, the agreement between Aβ1-42 and Aβ1-42/Aβ1-40 was 78.3%. The Aβ1-42/Aβ1-40 ratio showed a stronger correlation with tTau and pTau181 than Aβ1-42 and an agreement with tTau and pTau181 of 73.1% and 77.1%, respectively. Participants with a low Aβ1-42/Aβ1-40 ratio showed higher tTau and pTau181 and worse cognitive and functional prognosis, regardless of whether they were positive or negative for Aβ1-42. The results were consistent across stages, diagnostic categories, and use of different cutoffs., Conclusion: Although Aβ1-42 and Aβ1-42/Aβ1-40 are considered markers of the same pathophysiological pathway, our findings provide evidence favoring the use of the Aβ1-42/Aβ1-40 ratio in clinical laboratories in the context of AD., (© 2022. The Author(s).)
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- 2022
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46. Comparison of cerebrospinal fluid tau, ptau(181), synuclein, and 14-3-3 for the detection of Creutzfeldt-Jakob disease in clinical practice.
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Fayolle M, Lehmann S, and Delaby C
- Subjects
- 14-3-3 Proteins cerebrospinal fluid, Biomarkers cerebrospinal fluid, Humans, Sensitivity and Specificity, Synucleins, Creutzfeldt-Jakob Syndrome cerebrospinal fluid, Creutzfeldt-Jakob Syndrome diagnosis, tau Proteins cerebrospinal fluid
- Abstract
Creutzfeldt-Jakob disease (CJD) is the leading human prion disease and is a major public health concern, with the risk of secondary iatrogenic transmission. Screening for CJD is often based on the detection of 14-3-3 protein in cerebrospinal fluid (CSF) through western blot assay and, in a second step, on a more specific method such as RT-QuIC (Real-Time Quaking-Induced Conversion). Alternatives to the detection of 14-3-3 in CSF have recently been proposed, specifically CSF tau proteins, tau/p-tau(181) ratio, and alpha-synuclein. In the present work, we compare the diagnostic performance of these biomarkers with that of 14-3-3 protein in a cohort of suspected CJD patients. Our results indicate that tau detection is the most effective and suitable approach for routine disease detection in a clinical setting. Combination with other biomarkers does not improve overall performance, while the tau/p-tau(181) ratio remains useful for differentiating Alzheimer's from CJD. In the end, the performance of tau protein detection in CSF reached 78% sensitivity and 80% specificity for the detection of CJD. It is interesting to note that the use of an automated method with a high concentration range allows for rapid and accurate results, which is very useful in clinical practice and allows for confirmatory testing such as RT-QuIC without delay., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
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- 2022
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47. Cytokines as new biomarkers of skin wound vitality.
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Peyron PA, Colomb S, Becas D, Adriansen A, Gauchotte G, Tiers L, Marin G, Lehmann S, Baccino E, Delaby C, and Hirtz C
- Subjects
- Adult, Aged, Autopsy, Biomarkers, Female, Humans, Immunoassay, Male, Middle Aged, Predictive Value of Tests, Reproducibility of Results, Cytokines, Skin injuries, Wound Healing
- Abstract
Background: The diagnosis of skin wound vitality is currently based on standard histology, but histological findings lack sensitivity in case of a short survival time. New reliable biomarkers of vitality are therefore strongly needed. We assessed the ability of 10 candidate cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α) to discriminate between vital and early post-mortem wounds., Methods: Twenty-four cadavers with a recent open skin wound (< 3 h) were included (20 men, 4 women, mean age = 51.0 ± 24.3 years). An early post-mortem wound was performed in an uninjured skin area, and both wounds were sampled at the autopsy (post-mortem interval (PMI) = 66.3 ± 28.3 h). Needle-puncture sites related to resuscitation cares were included as very early post-mortem wounds (n = 6). In addition to standard histology, cytokines levels were simultaneously measured in each sample using a multiplex sandwich immunoassay, then normalized on healthy skin levels. A quantitative evaluation of IL-8-positive cells in ante- and post-mortem wound samples was also performed., Results: In the training set of samples (n = 72), cytokine levels were significantly higher in vital wounds (mean age = 47 ± 53 min) than in post-mortem wounds (mean PMI = 6.9 ± 9.0 h) (p < 0.2), except for two cytokines (IFN-γ and IL-2). IL-8 was the best discriminatory cytokine (Se = 54%, Sp = 100%, AUC = 0.79), while a multivariate model combining IL-4 and IL12p70 was a bit more discriminant (Se = 55%, Sp = 100%, AUC = 0.84). In the validation set (n = 72), the discriminatory power of the cytokines and the predictive model was slightly lower, with IL-8 remaining the best cytokine (Se = 46%, Sp = 96%, AUC = 0.75). The predictive model remained highly specific (Sp = 100%). Both the cytokines and the predictive model allowed the iatrogenic injuries to be correctly classified as post-mortem wounds. Standard histology and immunohistochemistry showed 21% sensitivity and a specificity of 79% and 100%, respectively. Only two iatrogenic wounds could be properly categorized histologically., Conclusion: This study suggests that cytokines could be useful biomarkers of skin wound vitality and that the immunoassay method could be more sensitive than immunohistochemistry to identify wounds with a short survival time. Further research is underway to confirm these preliminary data., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2021
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48. Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias.
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Alcolea D, Delaby C, Muñoz L, Torres S, Estellés T, Zhu N, Barroeta I, Carmona-Iragui M, Illán-Gala I, Santos-Santos MÁ, Altuna M, Sala I, Sánchez-Saudinós MB, Videla L, Valldeneu S, Subirana A, Pegueroles J, Hirtz C, Vialaret J, Lehmann S, Karikari TK, Ashton NJ, Blennow K, Zetterberg H, Belbin O, Blesa R, Clarimón J, Fortea J, and Lleó A
- Subjects
- Adult, Aged, Aged, 80 and over, Alzheimer Disease blood, Biomarkers blood, Cognitive Dysfunction blood, Female, Frontotemporal Dementia blood, Humans, Lewy Body Disease blood, Male, Middle Aged, Phosphorylation, Alzheimer Disease diagnosis, Amyloid beta-Peptides blood, Cognitive Dysfunction diagnosis, Frontotemporal Dementia diagnosis, Lewy Body Disease diagnosis, Neurofilament Proteins blood, tau Proteins blood
- Abstract
Objectives: All categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer's disease (AD) through an easy and minimally invasive approach., Methods: We measured Aβ, pTau181 and neurofilament light (NfL) in 150 plasma samples of the Sant Pau Initiative on Neurodegeneration cohort including patients with mild cognitive impairment, AD dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal participants. We classified participants in the AT(N) categories according to CSF biomarkers and studied the diagnostic value of plasma biomarkers within each category individually and in combination., Results: The plasma Aβ composite, pTau181 and NfL yielded areas under the curve (AUC) of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective A, T and N categories. The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A-T- participants. There was a moderate correlation between plasma Aβ composite and CSF Aβ1-42/Aβ1-40 (Rho=-0.5, p<0.001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p<0.001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p<0.001)., Conclusions: Plasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. A blood AT(N) signature may facilitate early diagnosis and follow-up of patients with AD through an easy and minimally invasive approach., Competing Interests: Competing interests: DA is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Pla Estratègic de Recerca i Innovació en Salut (PERIS SLT006/17/125), and from Instituto de Salud Carlos III (PI18/00435 and INT19/00016). He participated in advisory boards from Fujirebio-Europe and Roche Diagnostics and received speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia, Esteve and from Krka Farmacéutica S.L. CD is employed by Université de Montpellier and CHU de Montpellier. LM is employed by Biomedical Research Institute Sant Pau. ST is employed by Biomedical Research Institute Sant Pau. TE is employed by Biomedical Research Institute Sant Pau. Declarations of interest: Dr Estellés is funded by a 'Río Hortega' research grant from the Institute of Health Carlos III. NZ is employed by Hospital de la Santa Creu i Sant Pau. IB is employed by Hospital de la Santa Creu i Sant Pau. MC-I is employed by Hospital de la Santa Creu i Sant Pau. II-G is supported by the Global Brain Health Institute (Atlantic Fellow for Equity in Brain Health and pilot award for global brain health leaders GBHI ALZ UK-21-720973) and the 'Juan Rodés' grant from the Institute of Health Carlos III (JR20/00018). MAS-S is employed by Hospital de la Santa Creu i Sant Pau. He is funded by a 'Juan Rodés' research grant from the Institute of Health Carlos III. MA is employed by Biomedical Research Institute Sant Pau. Dr Altuna is funded by a 'Río Hortega' research grant from the Institute of Health Carlos III. IS is employed by Hospital de la Santa Creu i Sant Pau. MBS-S is employed by Biomedical Research Institute Sant Pau. LV is employed by Fundació Catalana Síndrome de Down. SV is employed by Biomedical Research Institute Sant Pau. AS is employed by Biomedical Research Institute Sant Pau. JP is employed by Biomedical Research Institute Sant Pau. CH is employed by Université de Montpellier et CHU de Montpellier. JV is employed by CHU de Montpellier. SL is employed by the University and the Hospital of Montpellier. He participated in advisory boards from Fujirebio-Europe and Roche. TKK is employed by the University of Gothenburg. NA is employed by the University of Gothenburg. KB is employed by Gothenburg University and Sahlgrenska University Hospital. KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. HZ is employed by the University of Gothenburg, Sahlgrenska University Hospital and University College London. HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. OB is employed by Biomedical Research Institute Sant Pau. Dr Belbin is funded by a 'Miguel Servet' research grant from the Institute of Health Carlos III. RB is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Institute of Health Carlos III, Fundació Bancària Obra Social La Caixa and Fundació La Marató de TV3. He participated in advisory boards from Lilly and Nutricia, and he received speaker honoraria and travel funding from Novartis and Nutricia. JC is employed by Biomedical Research Institute Sant Pau and received research grants from Generalitat de Catalunya and from Institute of Health Carlos III. JF is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Institute of Health Carlos III, Fundació La Marató de TV3, and Pla Estratègic de Recerca i Innovació en Salut (PERIS). AL is employed by Hospital de la Santa Creu i Sant Pau and received research grants from CIBERNED, Institute of Health Carlos III and Fundación BBVA. He participated in advisory boards from Fujirebio-Europe, Nutricia, Biogen, and received speaker honoraria from Lilly., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2021
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49. Tau protein in cerebrospinal fluid: a novel biomarker of the time of death?
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Peyron PA, Hirtz C, Baccino E, Ginestet N, Tiers L, Martinez AY, Lehmann S, and Delaby C
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- Aged, Aged, 80 and over, Biomarkers cerebrospinal fluid, Female, Humans, Male, Middle Aged, Postmortem Changes, tau Proteins cerebrospinal fluid
- Abstract
Background: Tau proteins are recognized biomarkers of neurodegeneration and neuronal damage in the cerebrospinal fluid (CSF). It has also been suggested that these CSF proteins could increase post-mortem due to neuronal death. The aim of this study was to investigate the changes in CSF total and phosphorylated tau (p-tau) levels in the early post-mortem interval (PMI), to determine whether these proteins could be relevant biomarkers of time since death., Methods: Tau and p-tau levels were measured by ELISA in lumbar and cisternal CSF samples from 82 corpses (46 men, 36 women, mean age: 72.4 ± 15.2 years) with a PMI < 12 h. Forty-eight of them were considered neurologically healthy at the time of death. Rectal and tympanic temperatures were also measured in 37 individuals, and two validated temperature-based methods of PMI estimation were applied (Henssge's nomogram and Baccino's method)., Results: CSF tau and p-tau levels were significantly increased, with respective median values of 3315 pg/mL and 68.5 pg/mL in the whole cohort, while lower but still increased levels were observed in neurologically healthy patients. Sub-occipital punctures systematically provided higher tau and p-tau values (p < 0.0001). Despite a great inter-individual variability, the concentrations of both biomarkers were positively correlated with the early PMI, with the highest correlation for cisternal p-tau (r = 0.50, p < 0.0001 in the whole cohort; r = 0.58, p = 0.0003 in the neurologically healthy patients). Higher levels of CSF biomarkers were observed for PMI > 6 h versus PMI ≤ 6 h, the discriminatory power of the biomarkers being higher in the subgroup of neurologically healthy patients. Based on cut-off values obtained by ROC curve analysis, the CSF biomarkers could rectify or adjust the time interval provided by the temperature-based methods in a significant number of cases. A predictive model combining tympanic temperature and cisternal tau values was found to be particularly accurate to assign individuals according to their PMI (≤ or > 6 h), with a Se of 83% and a Sp of 100% (AUC = 0.95)., Conclusion: Our findings suggest that CSF tau and p-tau proteins could serve as potential biomarkers of time since death, in association with tympanic temperature. The practical applicability of such an integrated approach has to be assessed by further studies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2021
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50. Analytical comparison of ELISA and mass spectrometry for quantification of serum hepcidin in critically ill patients.
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Delaby C, Vialaret J, Hirtz C, Lefebvre T, Herkert M, Puy H, Lasocki S, and Lehmann S
- Subjects
- Anemia, Iron-Deficiency blood, Anemia, Iron-Deficiency diagnosis, Critical Illness, Humans, Protein Isoforms blood, Reagent Kits, Diagnostic, Anemia, Iron-Deficiency etiology, Enzyme-Linked Immunosorbent Assay methods, Hepcidins blood, Mass Spectrometry methods
- Abstract
Aim: To compare methods of quantifying serum hepcidin (based on MS and ELISA) and their ability to diagnose true iron deficiency anemia in critically ill patients. Materials & methods: Serum hepcidin was measured in 119 critically ill patients included in the HEPCIDANE clinical trial, using either an ultra-sensitive ELISA kit (from DRG) or two different MS methods. Results: The results show a good correlation between the different methods studied. The Bland-Altman analysis and the Kappa test for clinical groups show a good or very good agreement between the different tests. Conclusion: ELISA or MS show a satisfactory commutability to quantify serum hepcidin. This is of great importance for the determination of therapeutic strategies in iron deficiency.
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- 2021
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