Intra-Individual Stability of CSF Biomarkers for Alzheimer's Disease over Two Years

Abstract

This study examines the intra-individual stability of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) over 2 years in 83 patients with mild cognitive impairment (MCI) and 17 cognitively healthy control individuals. All participants underwent clinical and neuropsychological evaluation and lumbar puncture at baseline and after 2 years at a university hospital memory clinic. CSF was analyzed for total tau (T-tau), phospho-tau₁₈₁ (P-tau₁₈₁) and amyloid-β_1–42 (Aβ_1–42). During the 2-year observational time, 12 MCI patients progressed to AD and 3 progressed to vascular dementia, while 68 remained stable. Baseline T-tau and P-tau₁₈₁ levels were elevated in the MCI-AD group as compared to the stable MCI patients and the control group ( $\mathit{p}\mathrm{<}0.01$ ), while baseline Aβ_1–42 levels were lower ( $\mathit{p}\mathrm{<}0.001$ ). Stable MCI patients were biochemically indistinguishable from controls. The biomarker levels at baseline and after 2 years showed Pearson R values between 0.81 and 0.91 ( $\mathit{p}\mathrm{<}0.001$ ) and coefficients of variation of 7.2 to 8.7%. In conclusion, intra-individual biomarker levels are remarkably stable over 2 years. Thus, even minor biochemical changes induced by treatment against AD should be detectable using these biomarkers, which bodes well for their usefulness as surrogate markers for drug efficacy in clinical trials.