The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer's disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is...

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Bibliographic Details
Published in:	Nature communications 2019-04, Vol.10 (1), p.1766-1766, Article 1766
Main Authors:	Franzmeier, Nicolai, Rubinski, Anna, Neitzel, Julia, Ewers, Michael
Format:	Article
Language:	eng
Subjects:	Adaptor Proteins, Signal Transducing - genetics Aged Aged, 80 and over Alleles Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer's disease Autopsy Brain Brain - diagnostic imaging Cognition Cognitive ability Cytoskeleton Cytoskeleton - metabolism Dementia disorders Endocytosis Female Gene polymorphism Genetic Variation Health risks Humans Magnetic Resonance Imaging Male Memory Nuclear Proteins - genetics Pathology Polymorphism Polymorphism, Single Nucleotide Positron emission tomography Risk analysis Risk Factors Single-nucleotide polymorphism Tau protein tau Proteins - metabolism Tumor Suppressor Proteins - genetics β-Amyloid
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Summary:	The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer's disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II-VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology.
ISSN:	2041-1723 2041-1723