Longitudinal CSF Alzheimer's disease biomarker changes from middle age to late adulthood

IntroductionWe examined longitudinal cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker changes among cognitively normal individuals with 10.7 years follow-up, on average. MethodsAnalyses included 278 participants (M age = 57.5 years); 94 have progressed from normal cognition to mild cognitive impairment (MCI). Amyloid beta (A beta)(42)/A beta(40), phosphorylated tau(181) (p-tau(181)), and total tau (t-tau) were measured using automated electrochemiluminescence assays. ResultsApolipoprotein E (APOE) epsilon 4 carriers had lower baseline A beta(42)/A beta(40), but longitudinal A beta(42)/A beta(40) decreases did not differ by APOE epsilon 4 after accounting for A beta(42)/A beta(40) positivity. Lower baseline A beta(42)/A beta(40) was associated with greater increases in tau (more strongly in males), and APOE epsilon 4 genotype was associated with greater tau increases after reaching A beta(42)/A beta(40) positivity. Participants who progressed to MCI had more abnormal biomarker levels and greater tau increases prior to MCI symptom onset. Biomarkers were more abnormal among older adults, but unrelated to sex or education. DiscussionOur results confirm accelerated biomarker changes during preclinical AD and highlight the important role of amyloid levels in tau accelerations.