title: Evaluation of CSF biomarkers as predictors of Alzheimer's disease: a clinical follow-up study of 4.7 years.
abstract: In this study, we determined the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers to predict development of Alzheimer's disease (AD) within five years in patients with mild cognitive impairment (MCI). To do so, the levels of tau, phosphorylated tau, Aβ42, Aβ40, Aβ38, sAβPPα, and sAβPPβ were analyzed in 327 CSF samples obtained at baseline from patients with AD (n = 94), MCI (n = 166), depressive disorder (n = 29), and cognitively healthy controls (n = 38). In the cohort with MCI at baseline, 33% subsequently developed AD and 16% developed other types of dementia; however, 51% were still cognitively stable after a followup of 4.7 years (range 3.0-7.2). Optimal cutoffs for each biomarker or combinations of biomarkers were defined in the AD, control, and depressive disorder groups. Several combinations resulted in sensitivity and specificity levels > 85% for differentiation of AD from controls and depressive disorder. Using the previously established cutoffs, a combination of Aβ42 and tau could predict future development of AD in MCI patients with a sensitivity of 88%, specificity 82%, positive predictive value 71%, and negative predictive value 94%. MCI patients with both low Aβ42 and high tau levels had a substantially increased risk of developing AD (OR 20; 95% CI 6-58), even after adjustment for confounding factors. Ultimately, CSF biomarkers can stratify MCI patients into those with very low or high risk for future development of AD. However, the specificities and positive predictive values are still too low to be able to diagnose AD before the patients fulfill the clinical criteria.
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Hertze
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Eugeen
authors.initials: E
authors.lastname: Vanmechelen
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins