title: Cystatin C levels are positively correlated with both Abeta42 and tau levels in cerebrospinal fluid in persons with Alzheimer's disease, mild cognitive impairment, and healthy controls.
abstract: Cystatin C is suggested to be involved in neurodegeneration and the development of Alzheimer's disease (AD) by binding to soluble amyloid-beta (Abeta) peptides. Studies of cystatin C levels in cerebrospinal fluid (CSF) in relation to risk of AD are conflicting and relations between cystatin C, Abeta42, and tau levels in CSF in AD, mild cognitive impairment (MCI), and healthy controls are unknown. The objective of this study was to investigate cystatin C, Abeta42, and tau levels in CSF in AD, MCI, and controls. As a secondary aim, the relationships between cystatin C, Abeta42, and tau levels across disease groups were investigated. Cystatin C, Abeta42, total tau, and phosphorylated tau levels in CSF were analyzed by turbidimetry (cystatin C) and xMAP Luminex technology (Abeta and tau) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Mean cystatin C levels were similar in cases of AD (5.6 micromol/L +/- 1.7), MCI (5.4 micromol/L +/- 1.48), and controls (5.6 micromol/L +/- 1.6). However, CSF cystatin C levels were strongly and positively correlated with total tau and phosphorylated tau levels (r=0.61-0.81, p< 0.0001) and Abeta42 (r=0.35-0.65, p< 0.001) independent of age, gender, and APOE genotype. Mean CSF cystatin C levels did not differ between patients with AD and MCI and healthy controls. Interestingly, cystatin C levels were positively correlated with both tau and Abeta42 levels in CSF independent of age, gender, and APOE genotype.
authors.affiliation: Uppsala University, Department of Public Health/Geriatrics, Uppsala, Sweden. johan.sundelof@pubcare.uu.se
authors.forename: Johan
authors.initials: J
authors.lastname: Sundelöf
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.forename: Maria
authors.initials: M
authors.lastname: Eriksdotter-Jönhagen
authors.forename: Vilmantas
authors.initials: V
authors.lastname: Giedraitis
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Malin
authors.initials: M
authors.lastname: Degerman-Gunnarsson
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Lena
authors.initials: L
authors.lastname: Kilander
authors.forename: Hans
authors.initials: H
authors.lastname: Basun
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000453:epidemiology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000453:epidemiology; D055316:Cystatin C / Q000134:cerebrospinal fluid*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D012307:Risk Factors; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins