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 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.
Skoog
I
I
Department of Clinical Neuroscience, University of Göteborg, Sweden.
Vanmechelen
E
E
Andreasson
L A
LA
Palmertz
B
B
Davidsson
P
P
Hesse
C
C
Blennow
K
K
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy / Q000134:cerebrospinal fluid / Q000235:genetics; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D011159:Population Surveillance; D014452:Ubiquitins / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D014452:Ubiquitins; D016875:tau Proteins