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Regulatory region genetic variation is associated with FYN expression in Alzheimer's disease
- 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.
- Subjects :
- Male
0301 basic medicine
Aging
Gene Expression
tau Proteins
Single-nucleotide polymorphism
Regulatory Sequences, Nucleic Acid
Biology
Proto-Oncogene Proteins c-fyn
Polymorphism, Single Nucleotide
environment and public health
Article
Cell Line
03 medical and health sciences
0302 clinical medicine
FYN
Alzheimer Disease
Gene expression
medicine
Humans
Phosphorylation
3' Untranslated Regions
Gene
Genetic Association Studies
Aged
Aged, 80 and over
Genetics
Messenger RNA
Kinase
Three prime untranslated region
General Neuroscience
Brain
Genetic Variation
medicine.disease
enzymes and coenzymes (carbohydrates)
030104 developmental biology
Haplotypes
Female
Neurology (clinical)
Geriatrics and Gerontology
Alzheimer's disease
030217 neurology & neurosurgery
Developmental Biology
Subjects
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