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The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological

Eleanna Kara1, Helen Ling, Alan M Pittman

  • 1Reta Lila Weston Laboratories and Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.

Neurobiology of Aging
|May 19, 2012
PubMed

Insights

A rare MAPT gene variant, p.A152T, is linked to frontotemporal dementia and other tauopathies. This variant may increase the risk for developing atypical neurodegenerative conditions involving tau accumulation.

Area of Science:

  • Neuroscience
  • Genetics
  • Pathology

Background:

  • Mutations in the Microtubule-Associated Protein Tau (MAPT) gene are implicated in frontotemporal dementia and various tauopathies.
  • Tauopathies are characterized by the accumulation of abnormal tau protein aggregates in the brain.

Purpose of the Study:

  • To investigate the role of a rare MAPT p.A152T variant in neurodegenerative diseases.
  • To determine if the p.A152T variant is associated with specific clinical presentations and pathological findings.

Main Methods:

  • Genetic screening of patients with parkinsonism, cognitive impairment, and neurofibrillary tangle pathology.
  • Clinical and pathological assessment of individuals carrying the MAPT p.A152T variant.

Main Results:

  • The p.A152T variant was identified in patients with parkinsonism, corticobasal degeneration, and Parkinson's disease with dementia.
  • The variant was also found in individuals with progressive cognitive impairment and in families with a history of neurodegeneration.
  • The p.A152T variant creates a new phosphorylation site, potentially affecting microtubule binding and promoting tau accumulation.

Conclusions:

  • The MAPT p.A152T variant is associated with a spectrum of neurodegenerative conditions characterized by abnormal tau accumulation.
  • This variant may act as a risk factor for developing atypical tauopathies with varied clinical phenotypes.
  • The p.A152T variant is not a fully penetrant pathogenic mutation but contributes to disease risk.

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