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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 < 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 …