Overexpression of four-repeat tau mRNA isoforms in progressive supranuclear palsy but not in Alzheimer's disease

Christopher B. Chambers, John M. Lee, Juan C Troncoso, Stephen Reich, Nancy A. Muma

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)325-332
Number of pages8
JournalAnnals of Neurology
Volume46
Issue number3
DOIs
StatePublished - 1999

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RNA Isoforms
Progressive Supranuclear Palsy
Neurofibrillary Tangles
Alzheimer Disease
tau Proteins
Frontal Lobe
Cerebellum
Brain Stem
Frontotemporal Dementia
Messenger RNA
Chromosomes, Human, Pair 17
Microtubule-Associated Proteins
Microtubules
Neurodegenerative Diseases
Protein Isoforms
Pathology
Mutation
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Overexpression of four-repeat tau mRNA isoforms in progressive supranuclear palsy but not in Alzheimer's disease. / Chambers, Christopher B.; Lee, John M.; Troncoso, Juan C; Reich, Stephen; Muma, Nancy A.

In: Annals of Neurology, Vol. 46, No. 3, 1999, p. 325-332.

Research output: Contribution to journalArticle

Chambers, Christopher B. ; Lee, John M. ; Troncoso, Juan C ; Reich, Stephen ; Muma, Nancy A. / Overexpression of four-repeat tau mRNA isoforms in progressive supranuclear palsy but not in Alzheimer's disease. In: Annals of Neurology. 1999 ; Vol. 46, No. 3. pp. 325-332.
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