The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aß-associated tau accumulation and cognitive decline.
Alzheimers Dement
; 18(1): 103-115, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34060233
ABSTRACT
INTRODUCTION:
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 (Aß), we tested whether BIN1 rs744373 accelerates Aß-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), Aß biomarkers, and longitudinal cognitive assessments. We assessed whether BIN1 rs744373 was associated with faster tau-PET accumulation at a given level of Aß 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 Aß by rs744373 interactions on global tau-PET change (ADNI ß/standard error [SE] = 0.42/0.14, P = 0.002; BioFINDER ß/SE = -0.35/0.15, P = .021), BIN1 risk-allele carriers showed accelerated tau-PET accumulation at higher Aß levels. In ADNI, rs744373 effects on cognitive decline were mediated by faster global tau-PET accumulation (ß/SE = 0.20/0.07, P = .005).DISCUSSION:
BIN1-associated AD risk is potentially driven by accelerated tau accumulation in the face of Aß.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Peptídeos beta-Amiloides
/
Proteínas tau
/
Polimorfismo de Nucleotídeo Único
/
Proteínas Supressoras de Tumor
/
Proteínas Adaptadoras de Transdução de Sinal
/
Doença de Alzheimer
/
Disfunção Cognitiva
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article