Elevated levels of tau in cerebrospinal fluid: Implications for the antemortem diagnosis of Alzheimer's disease

J. Q. Trojanowski, C. M. Clark, H. Arai, V. M.Y. Lee

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a heterogeneous group of dementias characterized by progressive cognitive impairments as well as by the accumulation of abundant extracellular deposits of Aβ and intra-neuronal neurofibrillary lesions in selectively vulnerable regions of the AD brain. The latter abnormalities (e.g. neurofibrillary tangles, dystrophic neurites, neuropil threads) are aggregates of paired helical filaments (PHFs) formed from altered tau proteins (PHFtau). Although PHFtau and normal central nervous system (CNS) tau are phosphorylated at nearly the same sites, PHFtau is phosphorylated to a greater extent, and alterations in the activity of CNS kinases and phosphatases most likely contribute to the pathogenesis of PHFtau. Since the abundance of neurofibrillary lesions correlates with the dementia in AD, the generation of PHFtau and the formation of neurofibrillary lesions may be part of a cell death pathway leading to massive neuron loss and dementia in AD. Building upon these and other insights into altered tau metabolism in AD, a series of studies suggest that the diagnosis of AD may be supported in living patients by determining the concentration of tau in cerebrospinal fluid (CSF). We review these promising studies here, and discuss them in the context of current understanding of the pathobiology of AD.

Original languageEnglish
Pages (from-to)297-305
Number of pages9
JournalJournal of Alzheimer's Disease
Volume1
Issue number4-5
DOIs
Publication statusPublished - 1999 Jan 1
Externally publishedYes

Keywords

  • Dementia
  • Neurofibrillary tangles
  • PHFs
  • PHFtau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Elevated levels of tau in cerebrospinal fluid: Implications for the antemortem diagnosis of Alzheimer's disease'. Together they form a unique fingerprint.

  • Cite this