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Regulatory region genetic variation is associated with FYN expression in Alzheimer's disease

Authors :
Maria Khrestian
Shane Formica
Thomas J. Montine
Lynn M. Bekris
Yvonne Shao
James B. Leverenz
McKenzie Shaw
Jeffrey A. Zahratka
Kaitlin Todd
Source :
Neurobiology of Aging. 51:43-53
Publication Year :
2017
Publisher :
Elsevier BV, 2017.

Abstract

Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau, are a key pathologic feature of Alzheimer's disease (AD). Tau phosphorylation is under the control of multiple kinases and phosphatases, including Fyn. Previously, our group found an association between 2 regulatory single nucleotide polymorphisms in the FYN gene with increased tau levels in the cerebrospinal fluid. In this study, we hypothesized that Fyn expression in the brain is influenced by AD status and genetic content. We found that Fyn protein, but not messenger RNA, levels were increased in AD patients compared to cognitively normal controls and are associated with regulatory region single nucleotide polymorphisms. In addition, the expression of the FYN 3'UTR can decrease expression in multiple cell lines, suggesting this regulatory region plays an important role in FYN expression. Taken together, these data suggest that FYN expression is regulated according to AD status and regulatory region haplotype, and genetic variants may be instrumental in the development of neurofibrillary tangles in AD and other tauopathies.

Details

ISSN :
01974580
Volume :
51
Database :
OpenAIRE
Journal :
Neurobiology of Aging
Accession number :
edsair.doi.dedup.....5912775236fb3b8a714bbfe2d690055f
Full Text :
https://doi.org/10.1016/j.neurobiolaging.2016.11.001