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

Alzheimer's disease (AD) is the most common form of dementia, and is c haracterized by a degeneration of neurones and their synapses, and a h igher 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 ta u 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 de mented (11 with probable Alzheimer's disease (AD), 13 with probable va scular 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 probab le VAD group (247 +/- 75 pg/mL; P < 0.005), than in the non-demented g roup (171 +/- 78 pg/mL), but did not significantly differ between the probable AD and probable VAD groups. In contrast, CSF-ubiquitin did no t significantly differ between the probable AD (100 +/- 24 ng/mL), pro bable VAD (102 +/- 16 ng/mL), and non-demented (97 +/- 27 ng/mL) group s. 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 apolip oprotein E E4 isoform. Higher CSF-tau and CSF-ubiquitin levels were al so associated with increasing degree of cortical and central brain atr ophy as measured by computerized tomography. The relationships between CSF-tau and severity of dementia and to brain atrophy suggest that CS F-tau may be used as a measure of neuronal/axonal degeneration in pati ents with dementia. We have previously shown a marked increase in both CSF-tau and CSF-ubiquitin in younger patients with AD and VAD. The le ss pronounced increase in CSF-tau and the lack of difference in CSF-ub iquitin in older patients suggest that the severity of the degenerativ e process is less in older than in younger demented patients. (C) 1995 Academic Press Limited.