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

Nicolai Franzmeier; Anna Rubinski; Julia Neitzel; Michael Ewers; Alzheimer’s Disease Neuroimaging Initiative (ADNI)

doi:10.1038/s41467-019-09564-5

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

Journal article

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

Nicolai Franzmeier, Anna Rubinski, Julia Neitzel, Michael Ewers and Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Nature communications, Vol.10(1), pp.1766-1766

04/16/2019

DOI: 10.1038/s41467-019-09564-5

PMCID: PMC6467911

PMID: 30992433

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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.

Magnetic Resonance Imaging

Brain - diagnostic imaging

Humans

Memory

Risk Factors

tau Proteins - metabolism

Male

Cognition

Positron-Emission Tomography

Genetic Variation

Endocytosis

Tumor Suppressor Proteins - genetics

Adaptor Proteins, Signal Transducing - genetics

Alleles

Alzheimer Disease - metabolism

Aged, 80 and over

Cytoskeleton - metabolism

Female

Aged

Polymorphism, Single Nucleotide

Alzheimer Disease - genetics

Nuclear Proteins - genetics

Details

Title: Subtitle: The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
Creators: Nicolai Franzmeier - Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377, Munich, Germany
Anna Rubinski - Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377, Munich, Germany
Julia Neitzel - Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377, Munich, Germany
Michael Ewers - Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377, Munich, Germany. michael.ewers@med.uni-muenchen.de
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: Nature communications, Vol.10(1), pp.1766-1766
DOI: 10.1038/s41467-019-09564-5
PMID: 30992433
PMCID: PMC6467911
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: England
Grant note: UL1 TR002369 / NCATS NIH HHS W81XWH-12-2-0012 / Department of Defense P30 AG008017 / NIA NIH HHS P30 AG010129 / NIA NIH HHS U01 AG024904 / NIA NIH HHS R01 AG054076 / NIA NIH HHS
Language: English
Date published: 04/16/2019
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051567502771

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