Longitudinal CSF Alzheimer's disease biomarker changes from middle age to late adulthood
Corinne Pettigrew, Anja Soldan, Jiangxia Wang, Mei‐Cheng Wang, Barry Greenberg, Marilyn Albert, Abhay Moghekar
Abstract
Abstract 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.