Longitudinal changes of CSF biomarkers in memory clinic patients

Objective: In Alzheimer disease ( AD), longitudinal changes of beta-amyloid(1-42) ( A beta(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 A beta(1-42), tau, and ptau-181 were measured. Results: CSF A beta(1-42) and tau levels showed main effects for both diagnosis and time ( all p < 0.05), with average increases of 47 +/- 72 and 49 +/- 143 pg/mL. The interaction terms were not significant, which implies a similar time effect for all diagnostic groups. CSF ptau-181 levels showed a main effect for diagnosis ( 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.