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The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline

Franzmeier, Nicolai ; Ossenkoppele, Rik LU ; Brendel, Matthias ; Rubinski, Anna ; Smith, Ruben LU ; Kumar, Atul LU orcid ; Mattsson-Carlgren, Niklas LU orcid ; Strandberg, Olof LU ; Duering, Marco and Buerger, Katharina , et al. (2022) In Alzheimer's and Dementia 18(1). p.103-115
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 (Aβ), we tested whether BIN1 rs744373 accelerates Aβ-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 18F-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... (More)

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 (Aβ), we tested whether BIN1 rs744373 accelerates Aβ-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 18F-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. Results: 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). Discussion: BIN1-associated AD risk is potentially driven by accelerated tau accumulation in the face of Aβ.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, amyloid, BIN1, tau
in
Alzheimer's and Dementia
volume
18
issue
1
pages
103 - 115
publisher
Wiley
external identifiers
  • scopus:85107294851
  • pmid:34060233
ISSN
1552-5260
DOI
10.1002/alz.12371
language
English
LU publication?
yes
additional info
Funding Information: ADNI data collection and sharing for this project was funded by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging, and Bioengineering, and through contributions from the following: AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol‐Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Phar‐ maceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann‐La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). Funding Information: The BioFINDER study was supported by the Swedish Research Council, the Knut and Alice Wallenberg foundation, the Marianne and Marcus Wallenberg foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, The Parkinson foundation of Sweden, The Parkinson Research Foundation, the Skåne University Hospital Foundation, and the Swedish federal government under the ALF agreement. The precursor of F‐flortaucipir was provided by AVID radiopharmaceuticals. 18 Funding Information: The study was funded by grants from the LMUexcellent and Legerlotz Foundations (to ME), LMU intramural funds (FöFoLe, 1032, awarded to NF), the Hertie foundation for clinical neurosciences (awarded to NF), the SyNergy excellence cluster (EXC 2145/ID 390857198), and the German Research Foundation (DFG, INST 409/193‐1 FUGG). Publisher Copyright: © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
id
6dd5b944-ec60-47d6-bcff-e831b3d930f7
date added to LUP
2021-06-24 14:23:13
date last changed
2024-06-15 12:56:29
@article{6dd5b944-ec60-47d6-bcff-e831b3d930f7,
  abstract     = {{<p>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 (Aβ), we tested whether BIN1 rs744373 accelerates Aβ-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 <sup>18</sup>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. Results: BIN1 rs744373 risk-allele carriers showed faster global tau-PET accumulation (ADNI/BioFINDER, P &lt;.001/P &lt;.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). Discussion: BIN1-associated AD risk is potentially driven by accelerated tau accumulation in the face of Aβ.</p>}},
  author       = {{Franzmeier, Nicolai and Ossenkoppele, Rik and Brendel, Matthias and Rubinski, Anna and Smith, Ruben and Kumar, Atul and Mattsson-Carlgren, Niklas and Strandberg, Olof and Duering, Marco and Buerger, Katharina and Dichgans, Martin and Hansson, Oskar and Ewers, Michael}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; amyloid; BIN1; tau}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{103--115}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline}},
  url          = {{http://dx.doi.org/10.1002/alz.12371}},
  doi          = {{10.1002/alz.12371}},
  volume       = {{18}},
  year         = {{2022}},
}