Variation in tau isoform expression in different brain regions and disease states

Elisa Majounie, William Cross, Victoria Newsway, Allissa Dillman, Jana Vandrovcova, Christopher M. Morris, Michael A. Nalls, Luigi Ferrucci, Michael J. Owen, Michael C. O'Donovan, Mark R. Cookson, Andrew B. Singleton, Rohan de Silva, Huw R. Morris

Research output: Contribution to journalArticlepeer-review

Abstract

Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian disorder. Abnormal tau inclusions, in selected regions of the brain, are a hallmark of the disease and the H1 haplotype of MAPT, the gene encoding tau, is the major risk factor in PSP. A 3-repeat and 4-repeat (4R) tau isoform ratio imbalance has been strongly implicated as a cause of disease. Thus, understanding tau isoform regional expression in disease and pathology-free states is crucial to elucidating the mechanisms involved in PSP and other tauopathies. We used a tau isoform-specific fluorescent assay to investigate relative 4R-tau expression in 6 different brain regions in PSP cases and healthy control samples. We identified a marked difference in 4R-tau relative expression, across brain regions and between MAPT haplotypes. Highest 4R-tau expression levels were identified in the globus pallidus compared with pons, cerebellum, and frontal cortex. 4R-tau expression levels were related to the MAPT H1 and H1c haplotypes. Similar regional variation was seen in PSP case and in control samples.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume34
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • MAPT
  • Progressive supranuclear palsy
  • Tauopathies

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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