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Overexpression of four‐repeat tau mRNA isoforms in progressive supranuclear palsy but not in Alzheimer's disease
Author(s) -
Chambers Christopher B.,
Lee John M.,
Troncoso Juan C.,
Reich Stephen,
Muma Nancy A.
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199909)46:3<325::aid-ana8>3.0.co;2-v
Subject(s) - progressive supranuclear palsy , gene isoform , tau protein , frontotemporal dementia , cerebellum , temporal cortex , brainstem , tauopathy , corticobasal degeneration , messenger rna , alzheimer's disease , neuroscience , biology , parkinsonism , pathology , dementia , disease , neurodegeneration , medicine , genetics , gene
Perturbations in the microtubule‐associated protein tau occur in several human neurodegenerative diseases. In Alzheimer's disease and progressive supranuclear palsy (PSP), tau proteins assemble into straight and paired helical filaments that form intraneuronal deposits of neurofibrillary tangles (NFTs). The mechanisms underlying the aberrant assembly of tau into NFTs is unknown. To determine whether alterations in the expression of the carboxyl‐terminal variants of tau contribute to NFT formation, we analyzed tau mRNA isoform expression in select regions of control, Alzheimer's disease, and PSP brains. In Alzheimer's disease, there were no alterations in tau mRNA isoform expression. However, in PSP, the levels of tau mRNA isoforms containing four microtubule binding domains were increased in the brainstem but not the frontal cortex or cerebellum. The brainstem in PSP has extensive NFT pathology, whereas the frontal cortex and cerebellum are relatively spared, suggesting that alterations in tau mRNA isoform expression occur in NFT‐vulnerable regions in this disease. An increase in the four‐repeat tau mRNA may lead to an increase in four‐repeat tau protein isoforms and may contribute to the formation of NFTs in PSP. A similar increase in four‐repeat tau mRNA has been reported for mutations associated with frontotemporal dementia and parkinsonism linked to chromosome 17.