期刊
NEUROBIOLOGY OF AGING
卷 33, 期 8, 页码 1591-1598出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.05.013
关键词
Alzheimer's disease; CSF biomarkers; Longitudinal
资金
- Pfizer
- Elan
- Janssen
- Danone Research
- Innogenetcs
- NeuroAdvisory Board
- Alzheimer Nederland and Stichting Vumc fonds
- Stichting Dioraphte
- Stichting De Merel
In this longitudinal study we investigated change over time in cerebrospinal fluid (CSF) levels of amyloid-beta 40 and 42 (A beta 40 and A beta 42), total tau (tau), tau phosphorylated at threonine 181 (ptau-181), isoprostane, neurofilaments heavy (NfH) and light (NfL). Twenty-four nondemented subjects, 62 mild cognitive impairment (MCI) and 68 Alzheimer's disease (AD) patients underwent 2 lumbar punctures, with minimum interval of 6, and a mean +/- SD of 24 +/- 13 months. Linear mixed models were used to assess change over time. Amyloid-beta 42, tau, and tau phosphorylated at threonine 181, differentiated between diagnosis groups (p < 0.05), whereas isoprostane, neurofilaments heavy, and NfL did not. In contrast, effects of follow-up time were only found for nonspecific CSF biomarkers: levels of NfL decreased, and levels of isoprostane, amyloid-beta 40, and tau increased over time (p < 0.05). Isoprostane showed the largest increase. In addition, increase in isoprostane was associated with progression of mild cognitive impairment to AD, and with cognitive decline as reflected by change in Mini Mental State Examination (MMSE). Contrary to AD-specific markers, nonspecific CSF biomarkers, most notably isoprostane, showed change over time. These markers could potentially be used to monitor disease progression in AD. (C) 2012 Elsevier Inc. All rights reserved.
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