Neurofibrillary tau pathology modulated by genetic variation of alpha-synuclein

Ann Neurol. 2008 Sep;64(3):348-52. doi: 10.1002/ana.21446.

Abstract

We analyzed whether genetic variation of alpha-synuclein modulates the extent of neuropathological changes in a population-based autopsied sample of 272 elderly Finns. None of the 11 markers was associated with the extent of neocortical beta-amyloid pathology. The intron 4 marker rs2572324 was associated with the extent of neurofibrillary pathology (p = 0.0006, permuted p = 0.004; Braak stages IV-VI vs 0-II). The same variant also showed a trend for association with neocortical Lewy-related pathology. These results suggest for the first time that variation of alpha-synuclein modulates neurofibrillary tau pathology and support the recent observations of an interaction of alpha-synuclein and tau in neurodegeneration.

MeSH terms

  • Aged, 80 and over
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Genetic Variation / genetics
  • Humans
  • Lewy Bodies / genetics
  • Lewy Bodies / metabolism
  • Lewy Bodies / pathology
  • Male
  • Neocortex / metabolism
  • Neocortex / pathology
  • Neocortex / physiopathology
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology*
  • Neurofibrillary Tangles / genetics
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology*
  • Neurons / metabolism
  • Neurons / pathology*
  • alpha-Synuclein / genetics*
  • tau Proteins / metabolism*

Substances

  • Genetic Markers
  • alpha-Synuclein
  • tau Proteins