Journal Article

DZNE-2021-00730

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline.

Franzmeier, N. (Corresponding author) ; Ossenkoppele, R. ; Brendel, M. ; Rubinski, A.Extern* ; Smith, R. ; Kumar, A. ; Mattsson-Carlgren, N. ; Strandberg, O. ; Duering, M. ; Bürger, K.DZNE* ; Dichgans, M.DZNE* ; Hansson, O. ; Ewers, M.DZNE* ; Initiative, , Alzheimer's Disease Neuroimaging ; study, t. S. B.

2022
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.12371

Abstract: 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.

Keyword(s): Adaptor Proteins, Signal Transducing: genetics (MeSH) ; Aged (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Brain: metabolism (MeSH) ; Cognitive Dysfunction: metabolism (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Nuclear Proteins: genetics (MeSH) ; Polymorphism, Single Nucleotide (MeSH) ; Positron-Emission Tomography (MeSH) ; Tumor Suppressor Proteins: genetics (MeSH) ; tau Proteins: metabolism (MeSH) ; Alzheimer's disease ; BIN1 ; amyloid ; tau

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Contributing Institute(s):

1. Coordinator of Clinical Parkinson Research (AG Höglinger 2)
2. Molecular Neurobiology (AG Simons)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2022

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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