Molecular analysis of mutant and wild-type tau deposited in the brain affected by the FTDP-17 R406W mutation

Am J Pathol. 2001 Feb;158(2):373-9. doi: 10.1016/S0002-9440(10)63979-X.


Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a familial neurological disorder, characterized genetically by autosomal dominant inheritance, clinically by behavioral abnormalities and parkinsonism, and neuropathologically by tauopathy. Linkage analyses of affected families have led to identification of several exonic and intronic mutations in the tau gene. In this study, we analyzed molecular species of tau in the soluble and insoluble fractions of brain affected by the FTDP-17 R406W mutation. Protein chemical analysis and Western blotting using site-specific antibodies indicated that almost equal amounts of wild-type and mutant tau were present in the Sarkosyl-insoluble fraction of the R406W brain. Consistent with this, wild-type and mutant tau colocalized in neurofibrillary tangles in the frontal cortex and hippocampus of the R406W brain. In contrast to soluble R406W tau, which was less phosphorylated than soluble wild-type tau, the Sarkosyl-insoluble mutant tau was highly phosphorylated as well as the insoluble wild-type tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Antibodies / immunology
  • Antibody Specificity
  • Blotting, Western
  • Brain / metabolism*
  • Brain / pathology
  • Genotype
  • Humans
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Mutation
  • Neurofibrillary Tangles / metabolism
  • Phosphorylation
  • tau Proteins / genetics*
  • tau Proteins / immunology
  • tau Proteins / metabolism


  • Antibodies
  • MAPT protein, human
  • Microtubule-Associated Proteins
  • tau Proteins