The Role of MAPT Haplotype H2 and Isoform 1N/4R in Parkinsonism of Older Adults
| Autor: | Lei Yu, Philip L. De Jager, Gyan Srivastava, David A. Bennett, Joshua M. Shulman, Guilherme T. Valenca, Julie A. Schneider, Aron S. Buchman, Jamary Oliveira-Filho, Charles C. White |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Myoclonus Male Movement disorders Molecular biology lcsh:Medicine Gene Expression Pathology and Laboratory Medicine 0302 clinical medicine Sequencing techniques Animal Cells Gene expression Diagnosis Medicine and Health Sciences Protein Isoforms lcsh:Science Neuropathology Genetics Neurons Aged 80 and over Multidisciplinary Movement Disorders Parkinsonism Age Factors Brain Neurodegenerative Diseases Parkinson Disease RNA sequencing Phenotype Neurology Female medicine.symptom Cellular Types Research Article medicine.medical_specialty Genotype Locus (genetics) tau Proteins Biology 03 medical and health sciences Signs and Symptoms Quantitative Trait Heritable Parkinsonian Disorders Diagnostic Medicine Internal medicine medicine Humans Genetic Predisposition to Disease Genetic Association Studies Aged Evolutionary Biology Population Biology Alternative splicing Haplotype lcsh:R Biology and Life Sciences Cell Biology medicine.disease Research and analysis methods Alternative Splicing 030104 developmental biology Endocrinology Molecular biology techniques Haplotypes Anatomical Pathology Cellular Neuroscience lcsh:Q Lewy Bodies 030217 neurology & neurosurgery Population Genetics Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 7, p e0157452 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Background and Objective Recently, we have shown that the Parkinson’s disease (PD) susceptibility locus MAPT (microtubule associated protein tau) is associated with parkinsonism in older adults without a clinical diagnosis of PD. In this study, we investigated the relationship between parkinsonian signs and MAPT transcripts by assessing the effect of MAPT haplotypes on alternative splicing and expression levels of the most common isoforms in two prospective clinicopathologic studies of aging. Materials and Methods using regression analysis, controlling for age, sex, study and neuropathology, we evaluated 976 subjects with clinical, genotyping and brain pathology data for haplotype analysis. For transcript analysis, we obtained MAPT gene and isoform-level expression from the dorsolateral prefrontal cortex for 505 of these subjects. Results The MAPT H2 haplotype was associated with lower total MAPT expression (p = 1.2x10-14) and global parkinsonism at both study entry (p = 0.001) and proximate to death (p = 0.050). Specifically, haplotype H2 was primarily associated with bradykinesia in both assessments (p |
| Databáze: | OpenAIRE |
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