The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

The Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Research output: Contribution to journalArticle

Abstract

The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology.

Original languageEnglish (US)
Article number1766
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

integrators
polymorphism
nucleotides
Polymorphism
genes
Single Nucleotide Polymorphism
Nucleotides
Genes
pathology
Pathology
Data storage equipment
Amyloid
brain
Brain
Alzheimer Disease
Alleles
sustaining
Memory Disorders
Endocytosis
Cytoskeleton

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory. / The Alzheimer’s Disease Neuroimaging Initiative (ADNI).

In: Nature communications, Vol. 10, No. 1, 1766, 01.12.2019.

Research output: Contribution to journalArticle

The Alzheimer’s Disease Neuroimaging Initiative (ADNI). / The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory. In: Nature communications. 2019 ; Vol. 10, No. 1.
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abstract = "The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology.",
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