A population-based study of tau protein and ubiquitin in cerebrospinal fluid in 85-year-olds: relation to severity of dementia and cerebral atrophy, but not to the apolipoprotein E4 allele

Neurodegeneration. 1995 Dec;4(4):433-42. doi: 10.1006/neur.1995.0052.


Alzheimer's disease (AD) is the most common form of dementia, and is characterized by a degeneration of neurones and their synapses, and a higher number of senile plaques (SP) and neurofibrillary tangles (NFT) compared with that found in non-demented individuals of the same age. NFT are composed of a hyperphosphorylated and ubiquitinated form of tau protein. Previous studies have found that in the cerebrospinal fluid (CSF) both tau and ubiquitin are increased in AD. We examined CSF-tau and CSF-ubiquitin in a population based sample of 85-year-olds, 26 demented (11 with probable Alzheimer's disease (AD), 13 with probable vascular dementia (VAD) and 2 with mixed (AD/VAD) type of dementia) and 35 non-demented individuals. CSF-tau was significantly higher both in the probable AD group (254 +/- 113 pg/mL; P < 0.01), and in the probable VAD group (247 +/- 75 pg/mL; P < 0.005), than in the non-demented group (171 +/- 78 pg/mL), but did not significantly differ between the probable AD and probable VAD groups. In contrast, CSF-ubiquitin did not significantly differ between the probable AD (100 +/- 24 ng/mL), probable VAD (102 +/- 16 ng/mL), and non-demented (97 +/- 27 ng/mL) groups. CSF-tau increased with increasing severity of dementia (P < 0.001), though no such relation was found for CSF-ubiquitin. Neither CSF-tau nor CSF-ubiquitin differed between patients with or without the apolipoprotein E E4 isoform. Higher CSF-tau and CSF-ubiquitin levels were also associated with increasing degree of cortical and central brain atrophy as measured by computerized tomography. The relationships between CSF-tau and severity of dementia and to brain atrophy suggest that CSF-tau may be used as a measure of neuronal/axonal degeneration in patients with dementia. We have previously shown a marked increase in both CSF-tau and CSF-ubiquitin in younger patients with AD and VAD. The less pronounced increase in CSF-tau and the lack of difference in CSF-ubiquitin in older patients suggest that the severity of the degenerative process is less in older than in younger demented patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Atrophy / cerebrospinal fluid
  • Atrophy / genetics
  • Brain / pathology*
  • Case-Control Studies
  • Dementia / cerebrospinal fluid*
  • Dementia / genetics
  • Dementia / pathology
  • Female
  • Humans
  • Male
  • Population Surveillance
  • Ubiquitins / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*


  • Apolipoprotein E4
  • Apolipoproteins E
  • Ubiquitins
  • tau Proteins