title: Hourly variability of cerebrospinal fluid biomarkers in Alzheimer's disease subjects and healthy older volunteers.
abstract: Large hour-to-hour variability has previously been demonstrated in the cerebrospinal fluid (CSF) concentrations of Alzheimer's disease (AD) biomarkers amyloid β(42) (Aβ(42)) and Aβ(40) in healthy younger subjects. We investigated the within-subject variability over 36 hours in CSF Aβ and tau proteins, in older subjects and AD patients. Six patients with mild stage AD (59-85 years, Mini Mental State Examination (MMSE) 16-26) and 6 healthy older volunteers (64-77 years) received an intrathecal catheter from which, during 36 hours, each hour 6 mL of CSF was drawn. Concentrations of Aβ(42), Aβ(40), total tau, and phosphorylated tau were determined and the variability was analyzed. Within-subject variability within 3-hour periods was assessed as the coefficient of variation, which was comparable for these 4 biomarkers in controls (4.2%-4.6%) and AD (3.1%-5.8%). Variability over 12 hour periods was 5.3% to 9.5%. These findings suggest that CSF biomarker variability is relatively low in healthy older controls and AD patients. Furthermore, continuous sampling of CSF proved to be a useful and robust method, which may also be used to investigate AD pathogenesis and to evaluate pharmacotherapeutic interventions.
authors: Department of Geriatric Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Diane
authors: D
authors: Slats
authors: Jurgen A H R
authors: JA
authors: Claassen
authors: Petra E
authors: PE
authors: Spies
authors: George
authors: G
authors: Borm
authors: Kees T C
authors: KT
authors: Besse
authors: William
authors: W
authors: van Aalst
authors: Jack
authors: J
authors: Tseng
authors: Magnus J C
authors: MJ
authors: Sjögren
authors: Marcel G M
authors: MG
authors: Olde Rikkert
authors: Marcel M
authors: MM
authors: Verbeek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins