TY  - JOUR
AU  - Franzmeier, Nicolai
AU  - Ossenkoppele, Rik
AU  - Brendel, Matthias
AU  - Rubinski, Anna
AU  - Smith, Ruben
AU  - Kumar, Atul
AU  - Mattsson-Carlgren, Niklas
AU  - Strandberg, Olof
AU  - Duering, Marco
AU  - Bürger, Katharina
AU  - Dichgans, Martin
AU  - Hansson, Oskar
AU  - Ewers, Michael
AU  - Initiative, , Alzheimer's Disease Neuroimaging
AU  - study, the Swedish BioFINDER
TI  - The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline.
JO  - Alzheimer's and dementia
VL  - 18
IS  - 1
SN  - 1552-5279
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2021-00730
SP  - 103-115
PY  - 2022
AB  - 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.
KW  - Adaptor Proteins, Signal Transducing: genetics
KW  - Aged
KW  - Alzheimer Disease: genetics
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Amyloid beta-Peptides: metabolism
KW  - Biomarkers: cerebrospinal fluid
KW  - Brain: metabolism
KW  - Cognitive Dysfunction: metabolism
KW  - Female
KW  - Humans
KW  - Male
KW  - Nuclear Proteins: genetics
KW  - Polymorphism, Single Nucleotide
KW  - Positron-Emission Tomography
KW  - Tumor Suppressor Proteins: genetics
KW  - tau Proteins: metabolism
KW  - Alzheimer's disease (Other)
KW  - BIN1 (Other)
KW  - amyloid (Other)
KW  - tau (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34060233
DO  - DOI:10.1002/alz.12371
UR  - https://pub.dzne.de/record/155552
ER  -