title: Longitudinal cerebrospinal fluid tau load increases in mild cognitive impairment.
abstract: Cross-sectional cerebrospinal fluid (CSF) levels of tau and amyloid (A) beta (beta) are of diagnostic importance for Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, most longitudinal studies of tau fail to demonstrate progression. Because predominantly brain-derived proteins such as tau, have higher ventricle to lumbar ratios, we hypothesized that adjusting for the ventricular enlargement of AD would correct for the dilution of tau, and improve detection of longitudinal change. Abeta which is not exclusively brain derived, shows a ratio <1, and no benefit was expected from adjustment. In a 1 year longitudinal study of eight MCI and ten controls, we examined CSF levels of hyperphosphorylated (P) tau231, Abeta40, and Abeta42. In cross-section, MCI patients showed elevated Ptau231 and Abeta40 levels, and greater ventricular volumes. Longitudinally, only after adjusting for the ventricular volume and only for Ptau231, were increases seen in MCI. Further studies are warranted on mechanisms of tau clearance and on using imaging to interpret CSF studies.
authors.affiliation: Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, NY 10016, USA. mony.deleon@med.nyu.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: de Leon
authors.forename: S
authors.initials: S
authors.lastname: Segal
authors.forename: C Y
authors.initials: CY
authors.lastname: Tarshish
authors.forename: S
authors.initials: S
authors.lastname: DeSanti
authors.forename: R
authors.initials: R
authors.lastname: Zinkowski
authors.forename: P D
authors.initials: PD
authors.lastname: Mehta
authors.forename: A
authors.initials: A
authors.lastname: Convit
authors.forename: C
authors.initials: C
authors.lastname: Caraos
authors.forename: H
authors.initials: H
authors.lastname: Rusinek
authors.forename: W
authors.initials: W
authors.lastname: Tsui
authors.forename: L A
authors.initials: LA
authors.lastname: Saint Louis
authors.forename: J
authors.initials: J
authors.lastname: DeBernardis
authors.forename: D
authors.initials: D
authors.lastname: Kerkman
authors.forename: F
authors.initials: F
authors.lastname: Qadri
authors.forename: A
authors.initials: A
authors.lastname: Gary
authors.forename: P
authors.initials: P
authors.lastname: Lesbre
authors.forename: T
authors.initials: T
authors.lastname: Wisniewski
authors.forename: J
authors.initials: J
authors.lastname: Poirier
authors.forename: P
authors.initials: P
authors.lastname: Davies
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000523:psychology; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012016:Reference Values; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D016875:tau Proteins