Increasing CSF phospho-tau levels during cognitive decline and progression to dementia

Neurobiol Aging. 2008 Oct;29(10):1466-73. doi: 10.1016/j.neurobiolaging.2007.03.027. Epub 2007 May 23.

Abstract

Background: Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression.

Objective: To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline.

Methods: Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM).

Results: There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up.

Conclusion: Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Biomarkers / analysis
  • Biomarkers / cerebrospinal fluid
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Cholinesterase Inhibitors / therapeutic use
  • Cognition Disorders / cerebrospinal fluid*
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology
  • Dementia / cerebrospinal fluid*
  • Dementia / pathology
  • Dementia / physiopathology
  • Disease Progression
  • Electroencephalography
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nerve Degeneration / cerebrospinal fluid*
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Neuropsychological Tests
  • Phosphorylation
  • Up-Regulation / physiology
  • tau Proteins / analysis
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Cholinesterase Inhibitors
  • MAPT protein, human
  • tau Proteins