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

被引：65

作者：

Skoog, I

Vanmechelen, E

Andreasson, LA

Palmertz, B

Davidsson, P

Hesse, C

Blennow, K

机构：

[1] GOTHENBURG UNIV, DEPT CLIN NEUROSCI, PSYCHIAT SECT, S-41124 GOTHENBURG, SWEDEN

[2] INNOGENET NV, GHENT, BELGIUM

[3] OSTRA HOSP, DEPT RADIOL, S-41685 GOTHENBURG, SWEDEN

[4] GOTHENBURG UNIV, DEPT CLIN NEUROSCI, NEUROCHEM UNIT, S-41124 GOTHENBURG, SWEDEN

来源：

NEURODEGENERATION | 1995年 / 4卷 / 04期

关键词：

Alzheimer's disease; apolipoprotein E; biochemical markers; cerebral atrophy; cerebrospinal fluid; computerized tomography of the brain; dementia; epidemiological methods; leukoaraiosis; tau protein; vascular dementia;

D O I：

10.1006/neur.1995.0052

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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. (C) 1995 Academic Press Limited.

引用

页码：433 / 442

页数：10

共 77 条

[1]

Ali-Khan Z., Normand J., Alizadeh-Khiavi K., Robitaille Y., Chronopoulos S., Ubiquitin profile and amyloid enhancing factor activity in Alzheimer and normal human brain extracts, Neurosci Lett, 139, pp. 24-28, (1992)

[2]

Diagnostic and Statistical Manual of Mental Disorders, (1987)

[3]

Blennow K., Wallin A., Clinical heterogeneity of probable Alzheimer's disease, J Geriatr Psychiatry Neurol, 5, pp. 106-113, (1992)

[4]

Blennow K., Fredman P., Wallin A., Gotffries C.G., Langstrom L., Svennerholm L., Protein analyses in cerebrospinal fluid: I. Influence of concentration gradients for proteins on cerebrospinal fluid/serum albumin ratio, Eur Neurol, 33, pp. 126-128, (1993)

[5]

Blennow K., Davidsson P., Wallin A., Gotffries C.G., Svennerholm L., Ubiquitin in cerebrospinal fluid in Alzheimer's disease and vascular dementia, Int Psychogeriatrics, 6, pp. 13-22, (1994)

[6]

Blennow K., Wallin A., Agren H., Spenger C., Siegfried J., Vanmechelen E., Tau protein in cerebrospinal fluid: A biochemical marker for axonal degeneration in Alzheimer's disease?, Mol Chem Neuropathol, (1995)

[7]

Bondareff W., Mountjoy C.Q., Roth M., Loss of neurons of origin of the adrenergic projection to cerebral cortex (Nucleus locus coeruleus) in senile dementia, Neurology, 32, pp. 164-168, (1982)

[8]

Coleman P.D., Flood D.G., Neuron numbers and dendrite extent in normal aging and Alzheimer's disease, Neurobiol Aging, 8, pp. 521-545, (1987)

[9]

Constantinidis J., Is Alzheimer's disease a major form of senile dementia? Clinical, anatomical and genetic data, Alzheimer's Disease: Senile Dementia and Related Disorders, 7, pp. 15-25, (1978)

[10]

Corder E.H., Saunders A.M., Strittmatter W.J., Schmechel D.E., Gaskell P.C., Small G.W., Roses A.D., Haines J.L., Pericak-Vance M.A., Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families, Science, 261, pp. 921-923, (1993)

← 1 2 3 4 5 6 7 8 →