Factors that influence the levels of cerebrospinal fluid biomarkers in memory clinic patients

Abstract

Background The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ), phospho tau (P-tau) and total tau (T-tau) are used increasingly to support a clinical diagnosis of Alzheimer’s disease. The diagnostic power of these biomarkers has been reported to vary among different studies’ results. The results are poorer when heterogeneous groups of patients have been included compared to studies where patients with Alzheimer’s dementia (AD) and healthy controls have been studied. The aim of this study was to examine if age, APOE genotype and sex were associated with the levels of CSF biomarkers among patients referred to a memory clinic.

Methods We included 257 patients from two memory clinics who had been assessed for dementia, including lumbar puncture.

Results The mean age of the patients was 68.1 (SD: 8.0) years; 50.2% were women and 66.5% were APOE ε4 positive. Of these patients, 80.5% were diagnosed with AD or amnestic MCI. Both APOE ε4 and increasing age were associated with decreasing levels of Aβ, but not the levels of the tau proteins. In multiple regression analyses, disease stage, defined as a MMSE ≥25 or <25, influenced factors associated with the CSF biomarkers. Among those with MMSE score ≥ 25, age, APOE ε4 genotype, and MMSE score, in addition to a diagnosis of AD, were associated with Aβ level, with an explained variance of 0.43. When using P-tau or T-tau as a dependent variable, the presence of one or two APOE ε4 alleles, and MMSE score influenced the results, in addition to the diagnosis of AD. The explained variance was lower for P-tau (0.26) and for T-tau (0.32). Among those with MMSE <25, these variables explained very little of the variance. There were no gender differences.

Conclusions We found that factors in addition to a diagnosis of AD, were associated with the levels of CSF biomarkers. Among those with MMSE ≥25, lower levels of Aβ were associated with several factors including increasing age. This is not reflected in clinical practice, where age-specific cutoffs exist only for T-tau. In this study, age was not associated with the levels of tau proteins.