%0 Journal Article
%A Franzmeier, Nicolai
%A Ossenkoppele, Rik
%A Brendel, Matthias
%A Rubinski, Anna
%A Smith, Ruben
%A Kumar, Atul
%A Mattsson-Carlgren, Niklas
%A Strandberg, Olof
%A Duering, Marco
%A Bürger, Katharina
%A Dichgans, Martin
%A Hansson, Oskar
%A Ewers, Michael
%A Initiative, , Alzheimer's Disease Neuroimaging
%A study, the Swedish BioFINDER
%T The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline.
%J Alzheimer's and dementia
%V 18
%N 1
%@ 1552-5279
%C Hoboken, NJ
%I Wiley
%M DZNE-2021-00730
%P 103-115
%D 2022
%X 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.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.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).BIN1-associated AD risk is potentially driven by accelerated tau accumulation in the face of Aβ.
%K Adaptor Proteins, Signal Transducing: genetics
%K Aged
%K Alzheimer Disease: genetics
%K Amyloid beta-Peptides: cerebrospinal fluid
%K Amyloid beta-Peptides: metabolism
%K Biomarkers: cerebrospinal fluid
%K Brain: metabolism
%K Cognitive Dysfunction: metabolism
%K Female
%K Humans
%K Male
%K Nuclear Proteins: genetics
%K Polymorphism, Single Nucleotide
%K Positron-Emission Tomography
%K Tumor Suppressor Proteins: genetics
%K tau Proteins: metabolism
%K Alzheimer's disease (Other)
%K BIN1 (Other)
%K amyloid (Other)
%K tau (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34060233
%R 10.1002/alz.12371
%U https://pub.dzne.de/record/155552