107 results on '"Schraen-Maschke S"'
Search Results
2. Overexpression of MBNL1 fetal isoforms and modified splicing of Tau in the DM1 brain: Two individual consequences of CUG trinucleotide repeats
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Dhaenens, C.M., Schraen-Maschke, S., Tran, H., Vingtdeux, V., Ghanem, D., Leroy, O., Delplanque, J., Vanbrussel, E., Delacourte, A., Vermersch, P., Maurage, C.A., Gruffat, H., Sergeant, A., Mahadevan, M.S., Ishiura, S., Buée, L., Cooper, T.A., Caillet-Boudin, M.L., Charlet-Berguerand, N., Sablonnière, B., and Sergeant, N.
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- 2008
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3. Apports de la biologie dans le diagnostic des démences
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Schraen-Maschke, S., Sergeant, N., Marzys, C., Bombois, S., Crinquette, C., Pasquier, F., Sablonnière, B., Buée, L., and Aubert, J. -P.
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- 2008
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4. Les marqueurs biochimiques du LCR : un outil diagnostique de la maladie d’Alzheimer
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Schraen-Maschke, S., Crinquette, C., Bombois, S., Pasquier, F., Delacourte, A., Buée, L., and Sablonnière, B.
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- 2007
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5. Absence of unidentified CAG repeat expansion in patients with Huntington's disease-like phenotype
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Vuillaume, I, Meynieu, P, Schraen-Maschke, S, Destée, A, and Sablonnière, B
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- 2000
6. Mis-splicing of Tau exon 10 in myotonic dystrophy type I is reproduced by overexpression of CELF2 but not by MBNL1 silencing
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Dhaenens, C.M., Tran, H., Frandemiche, M.-L., Carpentier, C., Schraen-Maschke, S., Sistiaga, A., Goicoechea, M., Eddarkaoui, S., Van Brussels, E., Obriot, H., Labudeck, A., Gevaert, M.H., Fernandez-Gomez, F., Charlet-Berguerand, N., Deramecourt, V., Maurage, C.A., Buée, Luc, De Munain, A. Lopez, Sablonnière, B., Caillet-Boudin, M.L., Sergeant, Nicolas, Peer, Hal, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Experimental Unit, Donostia Hospital, Neurological Unit, Département de neurologie [Lille], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Etude des mécanismes moléculaires à la base des dystrophies myotoniques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Département de neurologie[Lille], and Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
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musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,Neurofibrillary degeneration ,Microtubule-associated protein Tau ,CELF splicing factor family ,Myotonic dystrophy ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Triplet expansion disease ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Splicing ,MBNL1 - Abstract
International audience; Tau is the proteinaceous component of intraneuronal aggregates common to neurodegenerative diseases called Tauopathies, including myotonic dystrophy type I (DM1). In DM1, the presence of microtubule-associated protein Tau aggregates is associated with a mis-splicing of Tau. A toxic gain-of-function at the RNA level is a major etiological factor responsible for the mis-splicing of several transcripts in DM1. These are probably the consequence of a loss of MBNL1 function or gain of CELF1 splicing function. Whether these two dysfunctions occur together or separately, and whether all mis-splicing events in DM1 brain result from one or both of these dysfunctions remains unknown. Here, we analyzed the splicing of Tau exons 2 and 10 in the brain of DM1 patients. Two DM1 patients showed a mis-splicing of exon 10 whereas exon 2-inclusion was reduced in all DM1 patients. In order to determine the potential factors responsible for exon 10 mis-splicing, we studied the effect of the splicing factors MBNL1, CELF1, CELF2 and CELF4 or a dominant-negative CELF factor on Tau exon 10 splicing by ectopic expression or siRNA. Interestingly, the inclusion of Tau exon 10 is reduced by CELF2 whereas it is insensitive to the loss-of-function of MBNL1, CELF1 gain-of-function or a dominant-negative of CELF factor. Moreover, we observed an increased expression of CELF2 only in the brain of DM1 patients with a mis-splicing of exon 10. Taken together, our results indicate the occurrence of a mis-splicing event in DM1 that is neither induced by a loss of MBNL1 function nor a gain of CELF1 function, but is rather associated to CELF2 gain-of-function.
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- 2011
7. Tau exon 2 responsive elements deregulated in myotonic dystrophy type I are proximal to exon 2 and synergistically regulated by MBNL1 and MBNL2
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Carpentier, C., primary, Ghanem, D., additional, Fernandez-Gomez, F.J., additional, Jumeau, F., additional, Philippe, J.V., additional, Freyermuth, F., additional, Labudeck, A., additional, Eddarkaoui, S., additional, Dhaenens, C.M., additional, Holt, I., additional, Behm-Ansmant, I., additional, Marmier-Gourrier, N., additional, Branlant, C., additional, Charlet-Berguerand, N., additional, Marie, J., additional, Schraen-Maschke, S., additional, Buée, L., additional, Sergeant, N., additional, and Caillet-Boudin, M.L., additional
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- 2014
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8. Association of Plasma A beta Peptides with Blood Pressure in the Elderly
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Gravenor, MB, Lambert, J-C, Dallongeville, J, Ellis, KA, Schraen-Maschke, S, Lui, J, Laws, S, Dumont, J, Richard, F, Cottel, D, Berr, C, Ames, D, Masters, CL, Rowe, CC, Szoeke, C, Tzourio, C, Dartigues, J-F, Buee, L, Martins, R, Amouyel, P, Gravenor, MB, Lambert, J-C, Dallongeville, J, Ellis, KA, Schraen-Maschke, S, Lui, J, Laws, S, Dumont, J, Richard, F, Cottel, D, Berr, C, Ames, D, Masters, CL, Rowe, CC, Szoeke, C, Tzourio, C, Dartigues, J-F, Buee, L, Martins, R, and Amouyel, P
- Abstract
BACKGROUND: Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). METHODOLOGY/PRINCIPAL FINDINGS: Plasma Aß(1-40) and Aß(1-42) levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) and the Australian, longitudinal AIBL study (n = 576). In the combined sample, the Aß(1-42)/ Aß(1-40) ratio was significantly and inversely associated with SBP (p = 0.03) and a similar trend was observed for DBP (p = 0.06). Using the median age (69) as a cut-off, the Aß(1-42)/Aß(1-40) ratio was strongly associated with both SBP and DBP in elderly individuals (p = 0.002 and p = 0.03, respectively). Consistently, a high Aß(1-42)/ Aß(1-40) ratio was associated with a lower risk of hypertension in both the combined whole sample (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.56-0.90) and (to an even greater extent) in the elderly subjects (OR, 0.53; 95% CI, 0.37-0.75). Lastly, all these associations appeared to be primarily driven by the level of plasma Aß(1-40). CONCLUSION: The plasma Aß(1-42)/Aß(1-40) ratio is inversely associated with SBP, DBP and the risk of hypertension in elderly subjects, suggesting that Aß peptides affect blood pressure in vivo. These results may be particularly relevant in Alzheimer's disease, in which a high Aß(1-42)/Aß(1-40) plasma ratio is reportedly associated with a decreased risk of incident disease.
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- 2011
9. Mis-splicing of Tau exon 10 in myotonic dystrophy type 1 is reproduced by overexpression of CELF2 but not by MBNL1 silencing
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Dhaenens, C.M., primary, Tran, H., additional, Frandemiche, M.-L., additional, Carpentier, C., additional, Schraen-Maschke, S., additional, Sistiaga, A., additional, Goicoechea, M., additional, Eddarkaoui, S., additional, Van Brussels, E., additional, Obriot, H., additional, Labudeck, A., additional, Gevaert, M.H., additional, Fernandez-Gomez, F., additional, Charlet-Berguerand, N., additional, Deramecourt, V., additional, Maurage, C.A., additional, Buée, L., additional, de Munain, A. Lopez, additional, Sablonnière, B., additional, Caillet-Boudin, M.L., additional, and Sergeant, N., additional
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- 2011
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10. P18 Variant triplet repeats in the CTG expansion of DMPK affect stability of the expanded region and may contribute to unusual symptoms observed in some myotonic dystrophy type 1 cases
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Braida, C., primary, Stapleton, G., additional, Neil, F., additional, Rhadvanyi, H., additional, Philippe, C., additional, Finsterer, J., additional, Schraen-Maschke, S., additional, Gallano, P., additional, Warner, J., additional, Longman, C., additional, Hilton-Jones, D., additional, Brunner, H., additional, Kamsteeg, E.-J., additional, Berland, S., additional, Catalli, C., additional, Botta, A., additional, and Monckton, D.G., additional
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- 2010
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11. O2-5 Concordance de la tomographie cérébrale monophotonique de perfusion et des biomarqueurs du liquide céphalorachidien dans la maladie d’Alzheimer possible et probable
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Ravasi, L., primary, Bombois, S., additional, Semah, F., additional, Schraen-Maschke, S., additional, Buée, L., additional, Sablonnière, B., additional, Steinling, M., additional, and Pasquier, F., additional
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- 2009
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12. O1-5 Altération des concentrations plasmatiques des peptides amyloïdes dans les formes familiales de la maladie de Parkinson
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Duflot, A., primary, Schraen-Maschke, S., additional, Mutez, E., additional, Destée, A., additional, Buée, L., additional, and Chartier-Harlin, M.-C., additional
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- 2009
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13. P1-19 Dérégulation de l’épissage de Tau par MBNL1 dans une Tauopathie
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Tran, H., primary, Dhaenens, C.-M., additional, Trollet, C., additional, Obriot, H., additional, Ghanem, D., additional, Hammer, C., additional, Vanbrussels, E., additional, Charlet, N., additional, Gourdon, G., additional, Furling, D., additional, Buée, L., additional, Caillet-Boudin, M.-L., additional, Schraen-Maschke, S., additional, and Sergeant, N., additional
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- 2009
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14. C13 Intérêt des biomarqueurs du LCR et d’imagerie pour le diagnostic de la maladie d’Alzheimer
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Bombois, S., primary, Ravasi, L., additional, Delmaire, C., additional, Buée, L., additional, Schraen-Maschke, S., additional, and Pasquier, F., additional
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- 2009
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15. P2a-13 Biomarqueurs Tau, p-Tau et Aβ 1-42 dans le LCR : Proposition d’arbres décisionnels pour l’aide au diagnostic des démences et de la MA
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Schraen-Maschke, S., primary, Bombois, S., additional, Vercruysse, O., additional, Ravasi, L., additional, Pasquier, F., additional, Sablonnière, B., additional, and Buée, L., additional
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- 2009
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16. Association of plasma amyloid with risk of dementia: The prospective Three-City Study
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Lambert, J. -C., primary, Schraen-Maschke, S., additional, Richard, F., additional, Fievet, N., additional, Rouaud, O., additional, Berr, C., additional, Dartigues, J. -F., additional, Tzourio, C., additional, Alperovitch, A., additional, Buee, L., additional, and Amouyel, P., additional
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- 2009
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17. P1-5 Régulation de l’épissage alternatif des exons 2/3 et 6 des ARNm de Tau, deux processus d’épissage modifiés dans les cerveaux de patients atteints de Dystrophie myotonique de type 1
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Leroy, O., primary, Dhaenens, C.M., additional, Schraen-Maschke, S., additional, Maurage, C.A., additional, Buée, L., additional, Sablonnière, B., additional, Sergeant, N., additional, and Caillet-Boudin, M.L., additional
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- 2005
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18. Role of oligomannosidic N-glycans in the proliferation, adhesion and signalling of C6 glioblastoma cells
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Schraen-Maschke, S, primary
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- 2003
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19. Clinical features and genetic analysis of a new form of spinocerebellar ataxia
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Devos, D., primary, Schraen-Maschke, S., additional, Vuillaume, I., additional, Dujardin, K., additional, Naze, P., additional, Willoteaux, C., additional, Destee, A., additional, and Sablonniere, B., additional
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- 2001
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20. Association of plasma amyloid {beta} with risk of dementia: The prospective Three-City Study.
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Lambert JC, Schraen-Maschke S, Richard F, Fievet N, Rouaud O, Berr C, Dartigues JF, Tzourio C, Alpérovitch A, Buée L, and Amouyel P
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- 2009
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21. The first identified French family with dentatorubral-pallidoluysian atrophy.
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Destée, Alain, Delalande, Isabelle, Vuillaume, Isabelle, Schraen-Maschke, Susanna, Defebvre, Luc, Sablonnière, Bernard, Destée, A, Delalande, I, Vuillaume, I, Schraen-Maschke, S, Defebvre, L, and Sablonnière, B
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- 2000
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22. Biological markers in Alzheimer disease: what are the chances for less slow diagnosis? | Les marqueurs biologiques de la maladie d'Alzheimer: quel intérêt pour un diagnostic moins tardif?
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Schraen-Maschke, S., Dhaenens, C. M., Bombois, S., Deramecourt, V., Brussel, E., Obriot, H., Marzys, C., Sergeant, N., Maurage, C. A., Pasquier, F., Sablonnière, B., and Luc BUEE
23. Biochemical markers in the CSP: A diagnostic tool for Alzheimer's disease | Les marqueurs biochimiques du LCR: Un outil diagnostique de la maladie d'Alzheimer
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Schraen-Maschke, S., Crinquette, C., Bombois, S., Pasquier, F., Delacourte, A., Luc BUEE, and Sablonnière, B.
24. The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalene carboxylic acid can trigger apoptosis through a mitochondrial pathway independent of the nucleus
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Marchetti, P., Zamzami, N., Bertrand Joseph, Schraen-Maschke, S., Mereau-Richard, C., Costantini, P., Metivier, D., Susin, Sa, Kroemer, G., and Formstecher, P.
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Cell Nucleus ,Cytoplasm ,Cell-Free System ,Flavoproteins ,Transcription, Genetic ,Mitochondrial Permeability Transition Pore ,Receptors, Retinoic Acid ,Apoptosis Inducing Factor ,Membrane Proteins ,Antineoplastic Agents ,Apoptosis ,Endoplasmic Reticulum ,Mitochondrial Membrane Transport Proteins ,Ion Channels ,Mitochondria ,Retinoids ,Proto-Oncogene Proteins c-bcl-2 ,Tumor Cells, Cultured ,Humans - Abstract
The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalene carboxylic acid (AHPN/CD437), a retinoic acid receptor (RAR)gamma activator, has been found to inhibit the growth and to induce apoptosis of a wide variety of malignant cell types including solid tumors and various leukemias. Interestingly, CD437 is able to induce apoptosis in some all-trans-retinoic acid (ATRA)-resistant models. In a number of experimental systems, the early apoptotic stage that precedes nuclear chromatinolysis consists in mitochondrial alterations, including a disruption of the inner mitochondrial transmembrane potential (delta(psi)m) mediated by the mitochondrial permeability transition (MPT). Similarly CD437 causes RPMI 8226, a human myeloma cell line, to undergo a rapid delta(psi)m disruption that precedes other apoptotic alterations such as the generation of reactive oxygen species and DNA fragmentation. The same sequence of events is observed during the CD437-induced apoptosis in L363, a RARgamma-negative human myeloma cell line, as well as RPMI 8226 cytoplasts (anucleate cells). Indeed, RPMI 8226 cells and cytoplasts manifest a similar degree in delta(psi)m loss, phosphatidylserine exposure, and caspase activation in response to CD437, which indicates that nuclear effects cannot account for the apoptogenic potential of CD437. The mitochondrial release of cytochrome c, the activation of caspases as well as nuclear signs of CD437-induced apoptosis are fully prevented by the MPT inhibitory compound cyclosporin A. Purified mitochondria can be directly induced to undergo MPT with CD437 but not with ATRA. In a cell-free in vitro system consisting of exposing mitochondrial supernatants to isolated nuclei, only supernatants from CD437-treated mitochondria provoke chromatin condensation, whereas supernatants from mitochondria treated with ATRA, or with the combination of CD437 and cyclosporin A, remain inactive. In conclusion, these results suggest that the rapid execution of CD437-induced apoptosis is a nucleus-independent (and probably RARgamma-independent) phenomenon involving mitochondria and MPT.
25. 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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26. 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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27. 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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28. 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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29. 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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30. Plasma Aβ42/Aβ40 ratio is independent of renal function.
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Lehmann S, Schraen-Maschke S, Vidal JS, Allinquant B, Bombois S, Gabelle A, and Hanon O
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- Humans, Peptide Fragments, Kidney physiology, Amyloid beta-Peptides, Alzheimer Disease
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- 2023
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31. Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function.
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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, 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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32. Plasma amyloid beta predicts conversion to dementia in subjects with mild cognitive impairment: The BALTAZAR study.
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Hanon O, Vidal JS, Lehmann S, Bombois S, Allinquant B, Baret-Rose C, Tréluyer JM, Abdoul H, Gelé P, Delmaire C, Blanc F, Mangin JF, Buée L, Touchon J, Hugon J, Vellas B, Galbrun E, Benetos A, Berrut G, Paillaud E, Wallon D, Castelnovo G, Volpe-Gillot L, Paccalin M, Robert P, Godefroy O, Camus V, Belmin J, Vandel P, Novella JL, Duron E, Rigaud AS, Schraen-Maschke S, and Gabelle A
- Subjects
- Humans, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Peptide Fragments, tau Proteins, Disease Progression, Cognitive Dysfunction diagnosis, Alzheimer Disease diagnosis
- Abstract
Introduction: Blood-based biomarkers are the next challenge for Alzheimer's disease (AD) diagnosis and prognosis., Methods: Mild cognitive impairment (MCI) participants (N = 485) of the BALTAZAR study, a large-scale longitudinal multicenter cohort, were followed-up for 3 years. A total of 165 of them converted to dementia (95% AD). Associations of conversion and plasma amyloid beta (Aβ)
1-42 , Aβ1-40 , Aβ1-42 /Aβ1-40 ratio were analyzed with logistic and Cox models., Results: Converters to dementia had lower level of plasma Aβ1-42 (37.1 pg/mL [12.5] vs. 39.2 [11.1] , P value = .03) and lower Aβ1-42 /Aβ1-40 ratio than non-converters (0.148 [0.125] vs. 0.154 [0.076], P value = .02). MCI participants in the highest quartile of Aβ1-42 /Aβ1-40 ratio (>0.169) had a significant lower risk of conversion (hazard ratio adjusted for age, sex, education, apolipoprotein E ε4, hippocampus atrophy = 0.52 (95% confidence interval [0.31-0.86], P value = .01)., Discussion: In this large cohort of MCI subjects we identified a threshold for plasma Aβ1-42 /Aβ1-40 ratio that may detect patients with a low risk of conversion to dementia within 3 years., (© 2022 the Alzheimer's Association.)- Published
- 2022
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33. 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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34. 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
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- 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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35. 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.
- Published
- 2022
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36. Tau positron emission tomography, cerebrospinal fluid and plasma biomarkers of neurodegeneration, and neurocognitive testing: an exploratory study of participants with myotonic dystrophy type 1.
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Laforce RJ, Dallaire-Théroux C, Racine AM, Dent G, Salinas-Valenzuela C, Poulin E, Cayer AM, Bédard-Tremblay D, Rouleau-Bonenfant T, St-Onge F, Schraen-Maschke S, Beauregard JM, Sergeant N, and Puymirat J
- Subjects
- Adult, Amyloid beta-Peptides cerebrospinal fluid, Biomarkers, Humans, Positron-Emission Tomography methods, tau Proteins cerebrospinal fluid, Alzheimer Disease diagnosis, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction etiology, Myotonic Dystrophy complications, Myotonic Dystrophy diagnostic imaging
- Abstract
Objective: To investigate Tau pathology using multimodal biomarkers of neurodegeneration and neurocognition in participants with myotonic dystrophy type 1 (DM1)., Methods: We recruited twelve participants with DM1 and, for comparison, two participants with Alzheimer's Disease (AD). Participants underwent cognitive screening and social cognition testing using the Dépistage Cognitif de Québec (DCQ), among other tests. Biomarkers included Tau PET with [18F]-AV-1451, CSF (Aβ, Tau, phospho-Tau), and plasma (Aβ, Tau, Nf-L, GFAP) studies., Results: Of the twelve DM1 participants, seven completed the full protocol (Neurocognition 11/12; PET 7/12, CSF 9/12, plasma 12/12). Three DM1 participants were cognitively impaired (CI). On average, CI DM1 participants had lower scores on the DCQ compared to cognitively unimpaired (CU) DM1 participants (75.5/100 vs. 91.4/100) and were older (54 vs. 44 years old) but did not differ in years of education (11.3 vs. 11.1). The majority (6/7) of DM1 participants had no appreciable PET signal. Only one of the CI participants presented with elevated Tau PET SUVR in bilateral medial temporal lobes. This participant was the eldest and most cognitively impaired, and had the lowest CSF Aβ 1-42 and the highest CSF Tau levels, all suggestive of co-existing AD. CSF Tau and phospho-Tau levels were higher in the 3 CI compared to CU DM1 participants, but with a mean value lower than that typically observed in AD. Nf-L and GFAP were elevated in most DM1 participants (9/11 and 8/11, respectively). Finally, CSF phospho-Tau was significantly correlated with plasma Nf-L concentrations., Conclusions and Relevance: We observed heterogenous cognitive and biomarker profiles in individuals with DM1. While some participants presented with abnormal PET and/or CSF Tau, these patterns were highly variable and only present in a small subset. Although DM1 may indeed represent a non-AD Tauopathy, the Tau-PET tracer used in this study was unable to detect an in vivo Tau DM1 signature in this small cohort. Interestingly, most DM1 participants presented with elevated plasma Nf-L and GFAP levels, suggestive of other, possibly related, central brain alterations which motivate further research. This pioneering study provides novel insights towards the potential relationship between biomarkers and neurocognitive deficits commonly seen in DM1., (© 2022. The Author(s).)
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- 2022
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37. Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies.
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Leroux E, Perbet R, Caillierez R, Richetin K, Lieger S, Espourteille J, Bouillet T, Bégard S, Danis C, Loyens A, Toni N, Déglon N, Deramecourt V, Schraen-Maschke S, Buée L, and Colin M
- Subjects
- Brain metabolism, Humans, tau Proteins genetics, tau Proteins metabolism, Alzheimer Disease genetics, Alzheimer Disease pathology, Extracellular Vesicles metabolism, Tauopathies genetics, Tauopathies pathology
- Abstract
Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. Seed-competent tau species have been suggested to spread from cell to cell in a stereotypical manner, indicating that this may involve a prion-like mechanism. Although the intercellular mechanisms of transfer are unclear, extracellular vesicles (EVs) could be potential shuttles. We assessed this in humans by preparing vesicles from fluids (brain-derived enriched EVs [BD-EVs]). These latter were isolated from different brain regions in various tauopathies, and their seeding potential was assessed in vitro and in vivo. We observed considerable heterogeneity among tauopathies and brain regions. The most striking evidence was coming mainly from Alzheimer's disease where the BD-EVs clearly contain pathological species that can induce tau lesions in vivo. The results support the hypothesis that BD-EVs participate in the prion-like propagation of tau pathology among tauopathies, and there may be implications for diagnostic and therapeutic strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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38. Interactive pedagogical tools could be helpful for medical education continuity during COVID-19 outbreak.
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Grzych G and Schraen-Maschke S
- Subjects
- Betacoronavirus, COVID-19, Clinical Laboratory Services organization & administration, Computer-Assisted Instruction standards, Coronavirus Infections prevention & control, Disease Outbreaks, Education, Distance organization & administration, Education, Distance standards, Education, Medical, Continuing organization & administration, Humans, Internet organization & administration, Internet standards, Learning, Pandemics prevention & control, Pneumonia, Viral prevention & control, Problem-Based Learning methods, Problem-Based Learning organization & administration, Problem-Based Learning standards, SARS-CoV-2, Students, Medical psychology, Students, Medical statistics & numerical data, Video Recording methods, Video Recording standards, Computer-Assisted Instruction methods, Coronavirus Infections epidemiology, Education, Distance methods, Education, Medical, Continuing methods, Pneumonia, Viral epidemiology, Simulation Training methods, Simulation Training organization & administration, Simulation Training standards, Software
- Abstract
Training and education are essential for medical students. During the COVID-19 outbreak, numerous schools and universities have had to close. Ensuring pedagogical continuity requires alternatives to the traditional classroom, especially in medical education. Usual distance learning tools such as videos and downloadable handouts are not sufficient to promote efficient teaching. Distance learning requires self-motivation and does not give you direct access to your instructor. Some students fear the loss of human contact with an instructor - like asking questions during and after class - which promotes learning, understanding and communication. Moreover, classical distance learning methods do not offer immediate feedback that can help students in their understanding of the lecture. In this context, interactive pedagogic tools (IPT) could be useful for medical education continuity and for maintaining human contact necessary in pedagogy. We briefly evaluated interactive pedagogic tool compared to traditionnal distancial tools on medical students. This study showed the importance to have direct contact with a teacher and feedback during a lecture and to not exclusively perform distance learning without direct interaction and feedback. Hence, in the present context, we encourage teacher to use this type of tools to maintain direct interaction with students - which is essential in pedagogy - and ensure a qualitative pedagogical continuity.
- Published
- 2020
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39. From the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy.
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Colin M, Dujardin S, Schraen-Maschke S, Meno-Tetang G, Duyckaerts C, Courade JP, and Buée L
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- Animals, Humans, Proteostasis Deficiencies therapy, Tauopathies therapy, Immunotherapy methods, Proteostasis Deficiencies pathology, Tauopathies pathology
- Abstract
The term "propagon" is used to define proteins that may transmit misfolding in vitro, in tissues or in organisms. Among propagons, misfolded tau is thought to be involved in the pathogenic mechanisms of various "tauopathies" that include Alzheimer's disease, progressive supranuclear palsy, and argyrophilic grain disease. Here, we review the available data in the literature and point out how the prion-like tau propagation has been extended from Alzheimer's disease to tauopathies. First, in Alzheimer's disease, the progression of tau aggregation follows stereotypical anatomical stages which may be considered as spreading. The mechanisms of the propagation are now subject to intensive and controversial research. It has been shown that tau may be secreted in the interstitial fluid in an active manner as reflected by high and constant concentration of extracellular tau during Alzheimer's pathology. Animal and cell models have been devised to mimic tau seeding and propagation, and despite their limitations, they have further supported to the prion-like propagation hypothesis. Finally, such new ways of thinking have led to different therapeutic strategies in anti-tau immunotherapy among tauopathies and have stimulated new clinical trials. However, it appears that the prion-like propagation hypothesis mainly relies on data obtained in Alzheimer's disease. From this review, it appears that further studies are needed (1) to characterize extracellular tau species, (2) to find the right pathological tau species to target, (3) to follow in vivo tau pathology by brain imaging and biomarkers and (4) to interpret current clinical trial results aimed at reducing the progression of these pathologies. Such inputs will be essential to have a comprehensive view of these promising therapeutic strategies in tauopathies.
- Published
- 2020
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40. Interactive pedagogic tools: evaluation of three assessment systems in medical education.
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Grzych G and Schraen-Maschke S
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- Cell Phone, Educational Measurement standards, Humans, Inventions, Students, Medical, Students, Pharmacy, Surveys and Questionnaires, Virtual Reality, Education, Medical methods, Education, Medical standards, Educational Measurement methods, Problem-Based Learning methods, Problem-Based Learning standards, Simulation Training methods, Simulation Training standards, User-Computer Interface
- Abstract
Training in biology, pharmacy and medicine are essential in laboratory medicine in faculty and especially with recent residency modifications. Active learning improves critical thinking and is an essential component of health education. Interactive assessment systems for the interactive participation of students have emerged. Recently, many offers of audience response system (ARS) accessible by personal electronic devices such as smartphone, tablet or computer are available. These systems seem to be an effective teaching innovation according to students. We aimed to evaluate three pedagogical tools during real school lectures in order to be able to select them according to the needs: Votar, Socrative and Wooclap. Methods: Three connected participation tools will be tested during teaching at Lille University, faculty of pharmacy by 3 different teachers. 75 fifth-year pharmacy students divided into 2 groups of students will have attended at least one session using each of the systems studied. After lessons, an online questionnaire with 9 questions was submitted to students on their interest in each system. Questions measured student perception using a 1 to 10 scale. Results and discussion: 62 of 75 students completed online surveys and were included in the study. According students, ARS by smartphone or computer improve their education. Favorite application seems to be Socrative and Wooclap. This study provides student perception comparison of ARS. To complete, additional studies are needed to establish their efficacy after several month.
- Published
- 2019
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41. Corrigendum: Somatostatin and Neuropeptide Y in Cerebrospinal Fluid: Correlations With Amyloid Peptides Aß 1-42 , and Tau Proteins in Elderly Patients With Mild Cognitive Impairment.
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Duron E, Vidal JS, Grousselle D, Gabelle A, Lehmann S, Pasquier F, Bombois S, Buée L, Allinquant B, Schraen-Maschke S, Baret C, Rigaud AS, Hanon O, and Epelbaum J
- Abstract
[This corrects the article DOI: 10.3389/fnagi.2018.00297.].
- Published
- 2019
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42. Myotonic Dystrophy: an RNA Toxic Gain of Function Tauopathy?
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Fernandez-Gomez F, Tran H, Dhaenens CM, Caillet-Boudin ML, Schraen-Maschke S, Blum D, Sablonnière B, Buée-Scherrer V, Buee L, and Sergeant N
- Subjects
- Humans, Protein Isoforms chemistry, Protein Isoforms genetics, Protein Isoforms metabolism, tau Proteins chemistry, tau Proteins genetics, tau Proteins metabolism, Gain of Function Mutation, Myotonic Dystrophy genetics, Myotonic Dystrophy metabolism, RNA metabolism, Tauopathies genetics, Tauopathies metabolism
- Abstract
Myotonic dystrophies (DM) are rare inherited neuromuscular disorders linked to microsatellite unstable expansions in non-coding regions of ubiquitously expressed genes. The DMPK and ZNF9/CNBP genes which mutations are responsible for DM1 and DM2 respectively. DM are multisystemic disorders with brain affection and cognitive deficits. Brain lesions consisting of neurofibrillary tangles are often observed in DM1 and DM2 brain. Neurofibrillary tangles (NFT) made of aggregates of hyper and abnormally phosphorylated isoforms of Tau proteins are neuropathological lesions common to more than 20 neurological disorders globally referred to as Tauopathies. Although NFT are observed in DM1 and DM2 brain, the question of whether DM1 and DM2 are Tauopathies remains a matter of debate. In the present review, several pathophysiological processes including, missplicing, nucleocytoplasmic transport disruption, RAN translation which are common mechanisms implicated in neurodegenerative diseases will be described. Together, these processes including the missplicing of Tau are providing evidence that DM1 and DM2 are not solely muscular diseases but that their brain affection component share many similarities with Tauopathies and other neurodegenerative diseases. Understanding DM1 and DM2 pathophysiology is therefore valuable to more globally understand other neurodegenerative diseases such as Tauopathies but also frontotemporal lobar neurodegeneration and amyotrophic lateral sclerosis.
- Published
- 2019
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43. Somatostatin and Neuropeptide Y in Cerebrospinal Fluid: Correlations With Amyloid Peptides Aβ 1-42 and Tau Proteins in Elderly Patients With Mild Cognitive Impairment.
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Duron E, Vidal JS, Grousselle D, Gabelle A, Lehmann S, Pasquier F, Bombois S, Buée L, Allinquant B, Schraen-Maschke S, Baret C, Rigaud AS, Hanon O, and Epelbaum J
- Abstract
A combination of low cerebrospinal fluid (CSF) Amyloid β
1-42 (Aβ1-42 ) and high Total-Tau (T-Tau) and Phosphorylated-Tau (P-Tau) occurs at a prodromal stage of Alzheimer's disease (AD) and recent findings suggest that network abnormalities and interneurons dysfunction contribute to cognitive deficits. Somatostatin (SOM) and Neuropeptide Y (NPY) are two neuropeptides which are expressed in GABAergic interneurons with different fates in AD the former only being markedly affected. The aim of this study was to analyze CSF SOM, NPY and CSF Aβ1-42 ; T-Tau, P-Tau relationships in 43 elderly mild cognitively impairment (MCI) participants from the Biomarker of AmyLoïd pepTide and AlZheimer's disease Risk (BALTAZAR) cohort. In these samples, CSF SOM and CSF Aβ1-42 on the one hand, and CSF NPY and CSF T-Tau and P-Tau on the other hand are positively correlated. CSF SOM and NPY concentrations should be further investigated to determine if they can stand for early AD biomarkers. Clinical Trial Registration: www.ClinicalTrials.gov, identifier #NCT01315639.- Published
- 2018
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44. Plasma amyloid levels within the Alzheimer's process and correlations with central biomarkers.
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Hanon O, Vidal JS, Lehmann S, Bombois S, Allinquant B, Tréluyer JM, Gelé P, Delmaire C, Blanc F, Mangin JF, Buée L, Touchon J, Hugon J, Vellas B, Galbrun E, Benetos A, Berrut G, Paillaud E, Wallon D, Castelnovo G, Volpe-Gillot L, Paccalin M, Robert PH, Godefroy O, Dantoine T, Camus V, Belmin J, Vandel P, Novella JL, Duron E, Rigaud AS, Schraen-Maschke S, and Gabelle A
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Magnetic Resonance Imaging, Male, Mental Status and Dementia Tests statistics & numerical data, Middle Aged, Prospective Studies, Alzheimer Disease blood, Alzheimer Disease diagnosis, Amyloid beta-Peptides blood, Biomarkers blood, Biomarkers cerebrospinal fluid, Cognitive Dysfunction blood, Cognitive Dysfunction cerebrospinal fluid
- Abstract
Introduction: Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aβ
42 and Aβ40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers., Methods: One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included., Results: Plasma Aβ1-42 and Aβ1-40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aβ1-42 and P = .04 for Aβ1-40 ). Globally, plasma Aβ1-42 correlated with age, Mini-Mental State Examination, and APOE ε4 allele. Plasma Aβ1-42 correlated with all CSF biomarkers in MCI but only with CSF Aβ42 in AD., Discussion: Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
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45. Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy.
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Laurent C, Dorothée G, Hunot S, Martin E, Monnet Y, Duchamp M, Dong Y, Légeron FP, Leboucher A, Burnouf S, Faivre E, Carvalho K, Caillierez R, Zommer N, Demeyer D, Jouy N, Sazdovitch V, Schraen-Maschke S, Delarasse C, Buée L, and Blum D
- Subjects
- Aged, Animals, Cognitive Dysfunction therapy, Disease Models, Animal, Humans, Inflammation therapy, Mice, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Tauopathies therapy, Antibodies therapeutic use, CD3 Complex immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Cerebral Cortex immunology, Chemokines immunology, Cognitive Dysfunction immunology, Hippocampus immunology, Inflammation immunology, Tauopathies immunology
- Abstract
Alzheimer's disease is characterized by the combined presence of amyloid plaques and tau pathology, the latter being correlated with the progression of clinical symptoms. Neuroinflammatory changes are thought to be major contributors to Alzheimer's disease pathophysiology, even if their precise role still remains largely debated. Notably, to what extent immune responses contribute to cognitive impairments promoted by tau pathology remains poorly understood. To address this question, we took advantage of the THY-Tau22 mouse model that progressively develops hippocampal tau pathology paralleling cognitive deficits and reappraised the interrelationship between tau pathology and brain immune responses. In addition to conventional astroglial and microglial responses, we identified a CD8-positive T cell infiltration in the hippocampus of tau transgenic mice associated with an early chemokine response, notably involving CCL3. Interestingly, CD8-positive lymphocyte infiltration was also observed in the cortex of patients exhibiting frontemporal dementia with P301L tau mutation. To gain insights into the functional involvement of T cell infiltration in the pathophysiological development of tauopathy in THY-Tau22 mice, we chronically depleted T cells using anti-CD3 antibody. Such anti-CD3 treatment prevented hippocampal T cell infiltration in tau transgenic animals and reverted spatial memory deficits, in absence of tau pathology modulation. Altogether, these data support an instrumental role of hippocampal T cell infiltration in tau-driven pathophysiology and cognitive impairments in Alzheimer's disease and other tauopathies., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2017
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46. Aβ1-40 and Aβ1-42 Plasmatic Levels In Stroke: Influence of Pre-Existing Cognitive Status and Stroke Characteristics.
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Moulin S, Leys D, Schraen-Maschke S, Bombois S, Mendyk AM, Muhr-Tailleux A, Cordonnier C, Buee L, Pasquier F, and Bordet R
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- Aged, Aged, 80 and over, Cognition Disorders blood, Cohort Studies, Female, Humans, Male, Statistics, Nonparametric, Amyloid beta-Peptides blood, Cognition Disorders etiology, Peptide Fragments blood, Stroke blood, Stroke complications
- Abstract
Many stroke patients have pre-existing cognitive impairment. Plasma amyloid β peptides (Aβ) - possible biomarkers of Alzheimer's pathology - induce vascular dysfunction. Our objective was to evaluate factors influencing plasma Aβ1-40 and Aβ1-42 peptides in a cohort of stroke patients. In the Biostroke study (ClinicalTrials.gov Identifier: NCT00763217), we collected vascular risk factors, neuroimaging features and biological tests including Aβ1-40 and Aβ1-42. We used the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) to systematically assess the pre-existing cognitive status. Of 403 patients (371 ischemia), 25 met criteria for pre-existing dementia, 142 for pre-existing cognitive decline-no-dementia, and 236 had no PCoI. Aβ1-42 was independently associated with PCoI (odds ratio 0.973; 95% confidence interval: 0.950-0.996; p=0.024). Factors associated with plasma Aβ1- 40 were age, smoking and diabetes mellitus. After exclusion of hemorrhagic strokes, the results remained unchanged, but blood samples taken less than 12 hours after onset were associated with lower plasma Aβ1-40. Our results support a dissociated response of the 2 plasma Aβ peptides in stroke patients, plasma Aβ1-40 being involved in vascular aspects whereas Aβ1-42 might be involved in neurodegenerative processes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2017
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47. Tau Protein Quantification in Human Cerebrospinal Fluid by Targeted Mass Spectrometry at High Sequence Coverage Provides Insights into Its Primary Structure Heterogeneity.
- Author
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Barthélemy NR, Fenaille F, Hirtz C, Sergeant N, Schraen-Maschke S, Vialaret J, Buée L, Gabelle A, Junot C, Lehmann S, and Becher F
- Subjects
- Amino Acid Sequence, Biomarkers cerebrospinal fluid, Chromatography, Liquid, Humans, Molecular Sequence Data, Peptides chemistry, Reproducibility of Results, tau Proteins chemistry, Mass Spectrometry instrumentation, Mass Spectrometry methods, Peptides cerebrospinal fluid, tau Proteins cerebrospinal fluid
- Abstract
Tau protein plays a major role in neurodegenerative disorders, appears to be a central biomarker of neuronal injury in cerebrospinal fluid (CSF), and is a promising target for Alzheimer's disease immunotherapies. To quantify tau at high sensitivity and gain insights into its naturally occurring structural variations in human CSF, we coupled absolute quantification using protein standard with the multiplex detection capability of targeted high-resolution mass spectrometry (MS) on a Quadrupole-Orbitrap instrument. Using recombinant tau we developed a step-by-step workflow optimization including an extraction protocol that avoided affinity reagents and achieved the monitoring of 22 tau peptides uniformly distributed along the tau sequence. The lower limits of quantification ranged (LLOQ) from 150 to 1500 pg/mL depending on the peptide. Applied to endogenous CSF tau, up to 19 peptides were detected. Interestingly, there were significant differences in the abundance of peptides depending on their position in the sequence, with peptides from the tau mid-domain appearing significantly more abundant than peptides from the N- and C-terminus domains. This MS-based strategy provided results complementary to those of previous ELISA or Western Blot studies of CSF tau and could be applied to tau monitoring in human CSF cohorts.
- Published
- 2016
- Full Text
- View/download PDF
48. Differential Mass Spectrometry Profiles of Tau Protein in the Cerebrospinal Fluid of Patients with Alzheimer's Disease, Progressive Supranuclear Palsy, and Dementia with Lewy Bodies.
- Author
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Barthélemy NR, Gabelle A, Hirtz C, Fenaille F, Sergeant N, Schraen-Maschke S, Vialaret J, Buée L, Junot C, Becher F, and Lehmann S
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease diagnostic imaging, Amyloid beta-Peptides metabolism, Analysis of Variance, Chromatography, Liquid, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Mental Status Schedule, Middle Aged, Neuroimaging, Neuropsychological Tests, Peptide Fragments metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Statistics as Topic, Supranuclear Palsy, Progressive diagnostic imaging, Alzheimer Disease cerebrospinal fluid, Lewy Body Disease cerebrospinal fluid, Supranuclear Palsy, Progressive cerebrospinal fluid, tau Proteins cerebrospinal fluid
- Abstract
Microtubule-associated Tau proteins are major actors in neurological disorders, the so-called tauopathies. In some of them, and specifically in Alzheimer's disease (AD), hyperphosphorylated forms of Tau aggregate into neurofibrillary tangles. Following and understanding the complexity of Tau's molecular profile with its multiple isoforms and post-translational modifications represent an important issue, and a major analytical challenge. Immunodetection methods are, in fact, limited by the number, specificity, sensitivity, and capturing property of the available antibodies. Mass spectrometry (MS) has recently allowed protein quantification in complex biological fluids using isotope-labeled recombinant standard for absolute quantification (PSAQ). To study Tau proteins, which are found at very low concentrations within the cerebrospinal fluid (CSF), we relied on an innovative two-step pre-fractionation strategy, which was not dependent on immuno-enrichment. We then developed a sensitive multiplex peptide detection capability using targeted high-resolution MS to quantify Tau-specific peptides covering its entire sequence. This approach was used on a clinical cohort of patients with AD, progressive supranuclear palsy (PSP), and dementia with Lewy body (DLB) and with control non-neurodegenerative disorders. We uncovered a common CSF Tau molecular profile characterized by a predominance of central core expression and 1N/3R isoform detection. While PSP and DLB tau profiles showed minimal changes, AD was characterized by a unique pattern with specific modifications of peptide distribution. Taken together these results provide important information on Tau biology for future therapeutic interventions, and improved molecular diagnosis of tauopathies.
- Published
- 2016
- Full Text
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49. Association of plasma β-amyloid with MRI markers of structural brain aging the 3-City Dijon study.
- Author
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Kaffashian S, Tzourio C, Soumaré A, Dufouil C, Mazoyer B, Schraen-Maschke S, Buée L, and Debette S
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease blood, Alzheimer Disease etiology, Alzheimer Disease pathology, Biomarkers blood, Female, Follow-Up Studies, Hippocampus pathology, Humans, Male, Organ Size, Peptide Fragments blood, Aging blood, Aging pathology, Alzheimer Disease diagnosis, Amyloid beta-Peptides blood, Brain pathology, Magnetic Resonance Imaging
- Abstract
Cerebral β-amyloid (Aβ) deposition and atrophy are central features of Alzheimer disease. Studies of Alzheimer disease biomarkers have largely focused on Aβ in cerebrospinal fluid (CSF), and there is uncertainty as to what plasma Aβ may be a marker. We examined the association of Aβ levels in the plasma with magnetic resonance imaging (MRI)-markers of brain aging, including longitudinal changes in global and regional brain volumes, in dementia-free persons. We studied 1530 participants of the Three-City-Dijon cohort, aged 65-80 years. Plasma Aβ measurement and magnetic resonance imaging were performed at baseline and after a 4-year follow up. Total brain, gray matter, and hippocampal volume were estimated using voxel-based morphometry, and annualized change in brain volumes was calculated. Increased plasma Aβ1-40 was associated with lower baseline hippocampal volume. Although baseline plasma Aβ levels were not associated with longitudinal change in brain volumes, consistently high plasma Aβ1-40 levels were associated with faster total brain atrophy and consistently low plasma Aβ1-42/Aβ1-40 ratio, with increased total brain atrophy and gray matter atrophy. In dementia-free older adults, high plasma Aβ1-40 and low plasma Aβ1-42/Aβ1-40 ratio were associated with smaller hippocampal volume and accelerated global and regional brain atrophy respectively., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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50. Central Nervous System and Peripheral Inflammatory Processes in Alzheimer's Disease: Biomarker Profiling Approach.
- Author
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Delaby C, Gabelle A, Blum D, Schraen-Maschke S, Moulinier A, Boulanghien J, Séverac D, Buée L, Rème T, and Lehmann S
- Abstract
Brain inflammation is one of the hallmarks of Alzheimer disease (AD) and a current trend is that inflammatory mediators, particularly cytokines and chemokines, may represent valuable biomarkers for early screening and diagnosis of the disease. Various studies have reported differences in serum level of cytokines, chemokines, and growth factors in patients with mild cognitive impairment or AD. However, data were often inconsistent and the exact function of inflammation in neurodegeneration is still a matter of debate. In the present work, we measured the expression of 120 biomarkers (corresponding to cytokines, chemokines, growth factors, and related signaling proteins) in the serum of 49 patients with the following diagnosis distribution: 15 controls, 14 AD, and 20 MCI. In addition, we performed the same analysis in the cerebrospinal fluid (CSF) of 20 of these patients (10 AD and 10 controls). Among the biomarkers tested, none showed significant changes in the serum, but 13 were significantly modified in the CSF of AD patients. Interestingly, all of these biomarkers were implicated in neurogenesis or neural stem cells migration and differentiation. In the second part of the study, 10 of these putative biomarkers (plus 4 additional) were quantified using quantitative multiplex ELISA methods in the CSF and the serum of an enlarged cohort composed of 31 AD and 24 control patients. Our results confirm the potential diagnosis interest of previously published blood biomarkers, and proposes new ones (such as IL-8 and TNFR-I). Further studies will be needed to validate these biomarkers which could be used alone, combined, or in association with the classical amyloid and tau biomarkers.
- Published
- 2015
- Full Text
- View/download PDF
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