Title: Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology
Authors: Chapuis, J ×
Hansmannel, F
Gistelinck, Marc
Mounier, A
Van Cauwenberghe, C
Kolen, K V
Geller, F
Sottejeau, Y
Harold, D
Dourlen, P
Grenier-Boley, B
Kamatani, Y
Delepine, B
Demiautte, F
Zelenika, D
Zommer, N
Hamdane, M
Bellenguez, C
Dartigues, J-F
Hauw, J-J
Letronne, F
Ayral, A-M
Sleegers, K
Schellens, Annik
Broeck, L. V
Engelborghs, S
De Deyn, P P
Vandenberghe, R
O'Donovan, M
Owen, M
Epelbaum, J
Mercken, M
Karran, Eric
Bantscheff, M
Drewes, G
Joberty, G
Campion, D
Octave, J-N
Berr, C
Lathrop, M
Callaerts, Patrick
Mann, D
Williams, J
Buée, L
Dewachter, I
Van Broeckhoven, C
Amouyel, P
Moechars, D
Dermaut, B
Lambert, J-C
GERAD consortium #
Issue Date: Nov-2013
Publisher: Stockton Press
Series Title: Molecular Psychiatry vol:18 issue:11 pages:1225-1234
Article number: 10.1038/mp.2013.1
Abstract: Genome-wide association studies (GWAS) have identified a region upstream the BIN1 gene as the most important genetic susceptibility locus in Alzheimer's disease (AD) after APOE. We report that BIN1 transcript levels were increased in AD brains and identified a novel 3 bp insertion allele ∼28 kb upstream of BIN1, which increased (i) transcriptional activity in vitro, (ii) BIN1 expression levels in human brain and (iii) AD risk in three independent case-control cohorts (Meta-analysed Odds ratio of 1.20 (1.14-1.26) (P=3.8 × 10(-11))). Interestingly, decreased expression of the Drosophila BIN1 ortholog Amph suppressed Tau-mediated neurotoxicity in three different assays. Accordingly, Tau and BIN1 colocalized and interacted in human neuroblastoma cells and in mouse brain. Finally, the 3 bp insertion was associated with Tau but not Amyloid loads in AD brains. We propose that BIN1 mediates AD risk by modulating Tau pathology.
ISSN: 1359-4184
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Behavioral and Developmental Genetics
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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