6 results on '"Delaby C."'
Search Results
2. 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
-
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.
- Published
- 2022
3. Tau protein in cerebrospinal fluid: a novel biomarker of the time of death?
- Author
-
Peyron, PA, Hirtz, C, Baccino, E, Ginestet, N, Tiers, L, Martinez, AY, Lehmann, S, and Delaby, C
- Subjects
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
4. Detection of amyloid beta peptides in body fluids for the diagnosis of alzheimer's disease: Where do we stand?
- Author
-
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.
- Published
- 2020
5. Plasma and CSF biomarkers for the diagnosis of Alzheimer's disease in adults with Down syndrome: a cross-sectional study
- Author
-
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.
- Subjects
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
6. Diagnosis associated with Tau higher than 1200 pg/mL: Insights from the clinical and laboratory practice.
- Author
-
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.
- Subjects
- *
CEREBROSPINAL fluid , *NEUROFIBRILLARY tangles , *LEWY body dementia , *TAU proteins , *CREUTZFELDT-Jakob disease , *ALZHEIMER'S disease ,CENTRAL nervous system infections ,CENTRAL nervous system tumors - Abstract
Cerebrospinal fluid (CSF) biomarkers are valuable tools for the diagnosis of neurological diseases. We aimed to investigate within a retrospective multicentric study the final diagnosis associated with very high CSF Tau levels and to identify patterns of biomarkers that would differentiate them in clinical practice, to help clinical biologists into physicians' counseling. Within the national multicentric network ePLM, we included 1743 patients from January 1, 2008, to December 31, 2013, with CSF biomarkers assayed by the same Innotest assays (protein Tau, phospho-Tau [pTau], and Aβ 1-42). We identified 205 patients with protein Tau concentration higher than 1200 pg/mL and final diagnosis. Among those patients, 105 (51.2%) were suffering from Alzheimer's disease, 37 (18%) from sporadic Creuztfeldt-Jakob disease, and 63 (30.7%) from other neurological diseases including paraneoplastic/ central nervous system tumor, frontotemporal dementia, other diagnoses, amyloid angiopathy, Lewy body dementia, and infections of the central nervous system. Phospho-Tau, Aβ1-42 and Aβ1-42/pTau values differed significantly between the three groups of patients (p <.001). An Aβ1-42/pTau ratio between 4.7 and 9.7 was suggestive of other neurological diseases (threshold in AD: 8.3). CSF 14-3-3 was useful to discriminate Alzheimer's disease from Creuztfeldt-Jakob disease in case of Aβ1-42 concentrations <550 pg/mL or pTau>60 pg/mL. This work emphasizes the interest of a well-thought-out interpretation of CSF biomarkers in neurological diseases, particularly in the case of high Tau protein concentrations in the CSF. • Few patients (<10%) suspected of neurodegenerative diseases exhibit a CSF protein Tau concentration higher than 1200 pg/mL. • These patients mainly have Alzheimer disease, then Creutzfeld-Jakob disease, and for few other neurodegenerative and neurological diseases. • Current CSF biomarkers, including Amyloid beta 1-42, phosphoTau and the 14-3-3 are useful to differentiate those patients. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.