Advances in the development of biomarkers for Alzheimer's disease:: from CSF total tau and Aβ1-42 proteins to phosphorylated tau protein

被引:58
|
作者
Hampel, H
Goernitz, A
Buerger, K
机构
[1] Univ Munich, Dept Psychiat, Dementia Res Sect, D-80336 Munich, Germany
[2] Univ Munich, Alzheimer Mem Ctr, Memory Clin, D-80336 Munich, Germany
[3] Univ Munich, Geriatr Psychiat Branch, D-80336 Munich, Germany
关键词
mild cognitive impairment (MCI); biochemical markers; diagnosis; progression; dementia therapy; neurodegeneration;
D O I
10.1016/S0361-9230(03)00087-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Advances have been made to establish biological markers of Alzheimer's disease (AD). Measurement of total tau (t-tau) and beta-amyloid(1-42) (Abeta(1-42)) in the cerebrospinal fluid (CSF) seems useful to discriminate early and incipient AD from age-associated memory-impairment, depression, and some secondary dementias. New immunoassays to detect different phosphorylated tau epitopes (p-tau) have recently been developed. P-tau phosphorylated at threonine 231 (p-tau(231)) showed improvements compared to t-tau in the early detection of AD in subjects with mild cognitive impairment. As p-tau(231) declined during the course of AD, it may have potential to track disease progression. Additionally, p-tau231 improved differential diagnosis between AD, frontotemporal dementia, and geriatric major depression. P-tau phosphorylated at threonine 181 improved diagnostic accuracy between AD and dementia with Lewy bodies. P-tau phosphorylated at serine 199 demonstrated high discriminative power between AD and non-Alzheimer's dementia. P-tau phosphorylated at serine 306/serine 404 improved differential diagnosis between AD and vascular dementia. A comparative study of the different p-tau epitopes is currently under way. In summary, first clinical multi-center studies suggest that measurement of phosphorylated tau proteins may significantly improve early and differential diagnosis and may come close to fulfilling proposed criteria of a biological marker for AD. (C) 2003 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:243 / 253
页数:11
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