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

INTRODUCTION: We examined longitudinal cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker changes among cognitively normal individuals with 10.7 years follow‐up, on average. METHODS: Analyses included 278 participants (M age = 57.5 years); 94 have progressed from normal cognition to mild cognitive impairment (MCI). Amyloid beta (Aβ)(42)/Aβ(40), phosphorylated tau(181) (p‐tau(181)), and total tau (t‐tau) were measured using automated electrochemiluminescence assays. RESULTS: Apolipoprotein E (APOE) ε4 carriers had lower baseline Aβ(42)/Aβ(40), but longitudinal Aβ(42)/Aβ(40) decreases did not differ by APOE ε4 after accounting for Aβ(42)/Aβ(40) positivity. Lower baseline Aβ(42)/Aβ(40) was associated with greater increases in tau (more strongly in males), and APOE ε4 genotype was associated with greater tau increases after reaching Aβ(42)/Aβ(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. DISCUSSION: Our results confirm accelerated biomarker changes during preclinical AD and highlight the important role of amyloid levels in tau accelerations.