Longitudinal changes of CSF biomarkers in memory clinic patients

Objective: In Alzheimer disease (AD), longitudinal changes of beta-amyloid 1-42 (Aβ 1-42 ), tau, and phosphorylated tau at threonine 181 (ptau-181) in CSF have been reported in small studies only. We evaluated the natural course of CSF biomarkers in patients with AD, subjective complaints, and mild cognitive impairment (MCI). Methods: One hundred five patients (50 AD, 38 MCI, 17 subjective complaints) underwent two lumbar punctures, with a mean interval of 21 ± 9 months. CSF levels of Aβ 1-42 , tau, and ptau-181 were measured. Results: CSF Aβ 1-42 and tau levels showed main effects for both diagnosis and time (all p p = 0.01) but not for time ( p = 0.27, increase of 1.0 ± 12 pg/mL). Conclusion: Levels of CSF beta-amyloid 1-42 and tau but not phosphorylated tau at threonine 181 increased over time in this memory clinic patient cohort with comparable change in all diagnostic groups. The cross-sectional difference between diagnostic groups, however, exceeded by far the longitudinal changes within individuals, suggesting that these biomarkers are not sensitive as markers of disease progression.