title: Serial CSF sampling in Alzheimer's disease: specific versus non-specific markers.
abstract: In this longitudinal study we investigated change over time in cerebrospinal fluid (CSF) levels of amyloid-beta 40 and 42 (Aβ40 and Aβ42), 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.
authors: Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. m.kester@vumc.nl
authors: Maartje I
authors: MI
authors: Kester
authors: Peter G
authors: PG
authors: Scheffer
authors: Marleen J
authors: MJ
authors: Koel-Simmelink
authors: Harry
authors: H
authors: Twaalfhoven
authors: Nicolaas A
authors: NA
authors: Verwey
authors: Robert
authors: R
authors: Veerhuis
authors: Jos W
authors: JW
authors: Twisk
authors: Femke H
authors: FH
authors: Bouwman
authors: Marinus A
authors: MA
authors: Blankenstein
authors: Philip
authors: P
authors: Scheltens
authors: Charlotte
authors: C
authors: Teunissen
authors: Wiesje M
authors: WM
authors: van der Flier
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000150:complications; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers