Use of cerebrospinal fluid biomarker analysis for improving Alzheimer's disease diagnosis in a non-specialized setting.

Low levels of amyloid-β42 (Aβ42) 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, such as in Croatia, in order to improve the accuracy of AD diagnosis and to identify individuals with incipient AD. Using ELISA - enzyme-linked immunosorbent assay we analyzed CSF Aβ42, 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 Aβ42 (530 pg/mL) and high t-tau (350 pg/mL) or p181-tau (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 Aβ42 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%) and among patients with uncertain dementia (41.7%). APOE e4-allele was associated with the CSF biomarker changes typical for AD. This study shows that in a non-specialized setting CSF biomarker testing together with APOE genotyping may be used for improving the accuracy of AD diagnosis and for predicting individuals with incipient Alzheimer’s disease who need to receive further clinical follow-up.