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The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ‐associated tau accumulation and cognitive decline
Author(s) -
Franzmeier Nicolai,
Ossenkoppele Rik,
Brendel Matthias,
Rubinski Anna,
Smith Ruben,
Kumar Atul,
MattssonCarlgren Niklas,
Strandberg Olof,
Duering Marco,
Buerger Katharina,
Dichgans Martin,
Hansson Oskar,
Ewers Michael
Publication year - 2022
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12371
Subject(s) - positron emission tomography , alzheimer's disease neuroimaging initiative , cognitive decline , neuroimaging , single nucleotide polymorphism , allele , medicine , oncology , snp , cognition , alzheimer's disease , biology , psychology , neuroscience , disease , dementia , genetics , genotype , gene
The BIN1 rs744373 single nucleotide polymorphism (SNP) is a key genetic risk locus for Alzheimer's disease (AD) associated with tau pathology. Because tau typically accumulates in response to amyloid beta (Aβ), we tested whether BIN1 rs744373 accelerates Aβ‐related tau accumulation. Methods We included two samples (Alzheimer's Disease Neuroimaging Initiative [ADNI], n = 153; Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably [BioFINDER], n = 63) with longitudinal 18 F‐Flortaucipir positron emission tomography (PET), Aβ biomarkers, and longitudinal cognitive assessments. We assessed whether BIN1 rs744373 was associated with faster tau‐PET accumulation at a given level of Aβ and whether faster BIN1 rs744373‐associated tau‐PET accumulation mediated cognitive decline. Results BIN1 rs744373 risk‐allele carriers showed faster global tau‐PET accumulation (ADNI/BioFINDER, P < .001/ P < .001). We found significant Aβ by rs744373 interactions on global tau‐PET change (ADNI: β/standard error [SE] = 0.42/0.14, P = 0.002; BioFINDER: β/SE = –0.35/0.15, P = .021), BIN1 risk‐allele carriers showed accelerated tau‐PET accumulation at higher Aβ levels. In ADNI, rs744373 effects on cognitive decline were mediated by faster global tau‐PET accumulation (β/SE = 0.20/0.07, P = .005). Discussion BIN1 ‐associated AD risk is potentially driven by accelerated tau accumulation in the face of Aβ.