Send to

Choose Destination
Mol Psychiatry. 2013 Nov;18(11):1225-34. doi: 10.1038/mp.2013.1. Epub 2013 Feb 12.

Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology.

Author information

1] INSERM U744, Université Lille Nord de France, Institut pasteur de Lille, Lille, France [2] Université Lille Nord de France, Institut pasteur de Lille, Lille, France [3] Université Lille-Nord de France, Institut pasteur de Lille, Lille, France.


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.

[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center