Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

Amyloid-beta 42 (A beta 42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative...

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Autores: Jansen, RE, van der Lee, SJ, Gomez-Fonseca, D, de Rojas, I, Dalmasso, MC, Grenier-Boley, B, Zettergren, A, Mishra, A, Ali, M, Andrade, V, Bellenguez, C, Kleineidam, L, Kucukali, F, Sung, YJ, Tesi, N, Vromen, EM, Wightman, DP, Alcolea, D, Alegret, M, Alvarez, I, Amouyel, P, Athanasiu, L, Bahrami, S, Bailly, H, Belbin, O, Bergh, S, Bertram, L, Biessels, GJ, Blennow, K, Blesa, R, Boada, M, Boland, A, Buerger, K, Carracedo, A, Cervera-Carles, L, Chene, G, Claassen, JAHR, Debette, S, Deleuze, JF, de Deyn, PP, Diehl-Schmid, J, Djurovic, S, Dols-Icardo, O, Dufouil, C, Duron, E, Duzel, E, Fladby, T, Fortea, J, Frolich, L, Garcia-Gonzalez, P, Garcia-Martinez, M, Giegling, I, Goldhardt, O, Gobom, J, Grimmer, T, Haapasalo, A, Hampel, H, Hanon, O, Hausner, L, Heilmann-Heimbach, S, Helisalmi, S, Heneka, MT, Hernandez, I, Herukka, SK, Holstege, H, Jarholm, J, Kern, S, Knapskog, AB, Koivisto, AM, Kornhuber, J, Kuulasmaa, T, Lage, C, Laske, C, Leinonen, V, Lewczuk, P, Lleo, A, de Munain, AL, Lopez-Garcia, S, Maier, W, Marquie, M, Mol, MO, Montrreal, L, Moreno, F, Moreno-Grau, S, Nicolas, G, Nothen, MM, Orellana, A, Palhaugen, L, Papma, JM, Pasquier, F, Perneczky, R, Peters, O, Pijnenburg, YAL, Popp, J, Posthuma, D, Pozueta, A, Priller, J, Puerta, R, Quintela, I, Ramakers, I, Rodriguez-Rodriguez, E, Rujescu, D, Saltvedt, I, Sanchez-Juan, P, Scheltens, P, Scherbaum, N, Schmid, M, Schneider, A, Selbaek, G, Selnes, P, Shadrin, A, Skoog, I, Soininen, H, Tarraga, L, Teipel, S, Tijms, B, Tsolaki, M, Van Broeckhoven, C, Van Dongen, J, van Swieten, JC, Vandenberghe, R, Vidal, JS, Visser, PJ, Vogelgsang, J, Waern, M, Wagner, M, Wiltfang, J, Wittens, MMJ, Zetterberg, H, Zulaica, M, van Duijn, CM, Bjerke, M, Engelborghs, S, Jessen, F, Teunissen, CE, Pastor, P, Hiltunen, M, Ingelsson, M, Andreassen, OA, Clarimon, J, Sleegers, K, Ruiz, A, Ramirez, A, Cruchaga, C, Lambert, JC, van der Flier, W
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p13016
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13016
https://ddd.uab.cat/record/282303
Access Level:acceso abierto
Palabra clave:GWAS
Alzheimer's disease
Cerebrospinal fluid
Amyloid-beta
Tau
Descripción
Sumario:Amyloid-beta 42 (A beta 42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for A beta 42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple A beta 42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.

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