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

Authors

Nicolai Franzmeier, Klinikum der Universität München
Anna Rubinski, Klinikum der Universität München
Julia Neitzel, Klinikum der Universität München
Michael Ewers, Klinikum der Universität München
Michael W. Weiner, University of California, San Francisco
Paul Aisen, University of California, San Diego
Ronald Petersen, Mayo Clinic
Clifford R. Jack, Mayo Clinic
William Jagust, University of California, Berkeley
John Q. Trojanowski, University of Pennsylvania
Arthur W. Toga, University of Southern California
Laurel Beckett, University of California, Davis
Robert C. Green, Brigham and Women's Hospital
Andrew J. Saykin, Indiana University Bloomington
John Morris, Washington University in St. Louis
Leslie M. Shaw, University of Pennsylvania
Zaven Khachaturian, University of California, Davis
Greg Sorensen, Siemens AG
Lew Kuller, University of Pittsburgh
Marcus Raichle, Washington University in St. Louis
Steven Paul, Weill Cornell Medicine
Peter Davies, Albert Einstein College of Medicine of Yeshiva University
Howard Fillit, AD Drug Discovery Foundation
Franz Hefti, Acumen Pharmaceuticals
David Holtzman, Washington University in St. Louis
Marek M. Mesulam, Northwestern University
William Potter, National Institute of Mental Health (NIMH)
Peter Snyder, Brown University
Adam Schwartz, Eli Lilly and Company
Tom Montine, University of Washington, Seattle
Ronald G. Thomas, University of Washington, Seattle
Michael Donohue, University of Washington, Seattle

Document Type

Article

Publication Date

12-1-2019

Journal

Nature Communications

Volume

10

Issue

1

URL with Digital Object Identifier

10.1038/s41467-019-09564-5

Abstract

© 2019, The Author(s). 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.