Journal article

BDNF Val66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer's disease

Yen Ying Lim, Jason Hassenstab, Carlos Cruchaga, Alison Goate, Anne M Fagan, Tammie LS Benzinger, Paul Maruff, Peter J Snyder, Colin L Masters, Ricardo Allegri, Jasmeer Chhatwal, Martin R Farlow, Neill R Graff-Radford, Christoph Laske, Johannes Levin, Eric McDade, John M Ringman, Martin Rossor, Stephen Salloway, Peter R Schofield Show all

BRAIN | OXFORD UNIV PRESS | Published : 2016

Abstract

SEE ROGAEVA AND SCHMITT-ULMS DOI101093/AWW201 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate amyloid-β-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease. However, the effect of BDNF in autosomal dominant Alzheimer's disease is unknown. We aimed to determine the effect of BDNF Val66Met on cognitive function, hippocampal function, tau and amyloid-β in preclinical autosomal dominant Alzheimer's disease. We explored effects of apolipoprotein E (APOE) ε4 on these relationships. The Dominantl..

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Grants

Awarded by Dominantly Inherited Alzheimer's Network (DIAN) - National Institute on Aging (NIA)


Awarded by MRC Dementias Platform UK


Awarded by NCI Cancer Center Support Grant


Awarded by ICTS/CTSA from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH)



Awarded by MRC


Awarded by Medical Research Council


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer's Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA) and the German Center for Neurodegenerative Diseases (DZNE). This work was also supported by the NIHR Queen Square Dementia Biomedical Research Unit and the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1). We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant#UL1TR000448 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Data and/or tissue generated from DIAN fibroblasts (or IPSCs) and/or exome chip sequencing was supported by the DIAN-TU Pharma Consortium, (the DIAN-TU Pharma Consortium, http://dian-tu.wustl.edu/en/pharma-consortium-members/). This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. JP Chhatwal is supported by K23-AG049087. YY Lim is supported by the Alzheimer's Australia Dementia Research Fellowship, the Yulgilbar Alzheimer's Research Program, and the NHMRC-ARC Dementia Research Development Fellowship.