Serial CSF sampling in Alzheimer's disease: specific versus non-specific markers

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• 作者：Maartje I. Kester^a ; ^{m.kester@vumc.nl} ; Peter G. Scheffer^b ; Marleen J. Koel-Simmelink^b ; Harry Twaalfhoven^b ; Nicolaas A. Verwey^a ; ^b ; Robert Veerhuis^b ; Jos W. Twisk^c ; Femke H. Bouwman^d ; Marinus A. Blankenstein^b ; Philip Scheltens^a ; Charlotte Teunissen^b ; Wiesje M. van der Flier^a ; ^c
• 关键词：Alzheimer's disease ; CSF biomarkers ; Longitudinal
• 刊名：Neurobiology of Aging
• 出版年：2012
• 期刊代码：202_01974580
• 类别：med
• 出版时间：August, 2012
• 卷：33
• 期：8
• 页码：1591-1598
• 文件大小：549 K

摘要

In this longitudinal study we investigated change over time in cerebrospinal fluid (CSF) levels of amyloid-beta 40 and 42 (A尾40 and A尾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 卤 SD of 24 卤 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.