Journal
ALZHEIMERS & DEMENTIA
Volume 18, Issue 1, Pages 103-115Publisher
WILEY
DOI: 10.1002/alz.12371
Keywords
Alzheimer' s disease; amyloid; BIN1; tau
Categories
Funding
- LMUexcellent Foundation
- Legerlotz Foundation
- LMU intramural funds (FoFoLe) [1032]
- Hertie foundation for clinical neurosciences
- SyNergy excellence cluster [EXC 2145, 390857198]
- German Research Foundation (DFG) [INST 409/193-1 FUGG]
- Swedish Research Council
- Knut and Alice Wallenberg foundation
- Marianne and MarcusWallenberg foundation
- Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University
- Swedish Alzheimer Foundation
- Swedish Brain Foundation
- Parkinson fundation of Sweden,
- Parkinson Research Foundation
- Skane University Hospital Foundation
- Swedish federal government under the ALF agreement
- ADNI (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense award) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- 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
- 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
- Transition Therapeutics
- Canadian Institutes of Health Research
Ask authors/readers for more resources
The study found that carriers of the BIN1 rs744373 risk allele showed faster global tau-PET accumulation and accelerated tau-PET accumulation at higher A beta levels. In the ADNI sample, the effects of rs744373 on cognitive decline were mediated by faster global tau-PET accumulation.
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 (A beta), we tested whether BIN1 rs744373 accelerates A beta-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 F-18-Flortaucipir positron emission tomography (PET), A beta biomarkers, and longitudinal cognitive assessments. We assessed whether BIN1 rs744373 was associated with faster tau-PET accumulation at a given level of A beta 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 P < .001). We found significant A beta by rs744373 interactions on global tau-PET change (ADNI: beta/standard error [SE] = 0.42/0.14, P = 0.002; BioFINDER: beta/SE = -0.35/0.15, P = .021), BIN1 risk-allele carriers showed accelerated tau-PET accumulation at higher A beta levels. In ADNI, rs744373 effects on cognitive decline were mediated by faster global tau-PET accumulation (beta/SE = 0.20/0.07, P = .005). Discussion BIN1-associated AD risk is potentially driven by accelerated tau accumulation in the face of A beta.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available