title: Use of cerebrospinal fluid biomarker analysis for improving Alzheimer's disease diagnosis in a non-specialized setting.
abstract: Low levels of amyloid-beta42 (Abeta42) and high total-tau (t-tau) or phosphorylated-tau (p181-tau) levels in cerebrospinal fluid (CSF) were shown to be characteristic for Alzheimer's disease (AD) patients and for mildly cognitively impaired (MCI) or non-demented individuals who will progress to AD. The goal of this study was to evaluate the benefit of CSF biomarker testing in a setting with no specialized dementia centers, in order to improve the accuracy of AD diagnosis and to identify individuals with incipient AD. Using ELISA assay we analyzed CSF Abeta42, t-tau and p181-tau levels among clinically diagnosed non-demented individuals, AD patients and individuals with uncertain dementia (n=36). CSF cut-off values of low Abeta42 (less than or equal to 530 pg/mL) and high t-tau (less than or equal to 350 pg/mL) or p181-tau (less than or equal to 52 pg/mL) were used to identify individuals with AD/MCI-CSF profile, regardless of clinical diagnosis. APOE genotyping was performed using PCR-RFLP method. In accord with previous studies we detected significantly decreased levels of CSF Abeta42 and increased tau and p181-tau levels in clinically diagnosed AD group vs. non-demented controls. CSF profiling identified individuals with a typical AD/MCI-CSF pattern in clinically referred non-demented group (9 percent) and among patients with uncertain dementia (41.7 percent). APOE epsilon4-allele was associated with the CSF biomarker changes typical for AD. This study shows that in a non-specialized setting CSF biomarker testing may be used as a screening tool for improving the accuracy of AD diagnosis and for predicting individuals with incipient Alzheimer's disease who need to receive further clinical follow-up.
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Martina
authors.initials: M
authors.lastname: Malnar
authors.forename: Marko
authors.initials: M
authors.lastname: Kosicek
authors.forename: Raphael
authors.initials: R
authors.lastname: Bene
authors.forename: Iva Petek
authors.initials: IP
authors.lastname: Tarnik
authors.forename: Sanda
authors.initials: S
authors.lastname: Pavelin
authors.forename: Ivana
authors.initials: I
authors.lastname: Babic
authors.forename: Bojana
authors.initials: B
authors.lastname: Brajenovic-Milic
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Hecimovic
authors.forename: Marina
authors.initials: M
authors.lastname: Titlic
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trkanjec
authors.forename: Ida
authors.initials: I
authors.lastname: Demarin
authors.forename: Silva
authors.initials: S
authors.lastname: Hecimovic
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D016875:tau Proteins