Plasma Alzheimer's disease biomarker variability: Amyloid-independent and amyloid-dependent factors

초록

INTRODUCTIONWe aimed to investigate which factors affect plasma biomarker levels via amyloid beta (A beta)-independent or A beta-dependent effects and improve the predictive performance of these biomarkers for A beta positivity on positron emission tomography (PET). METHODSA total of 2935 participants underwent blood sampling for measurements of plasma A beta 42/40 ratio, phosphorylated tau 217 (p-tau217; ALZpath), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels using single-molecule array and A beta PET. Laboratory findings were collected using a routine blood test battery. RESULTSA beta-independent factors included hemoglobin and estimated glomerular filtration rate (eGFR) for p-tau217 and hemoglobin, eGFR, and triiodothyronine (T3) for GFAP and NfL. A beta-dependent factors included apolipoprotein E genotypes, body mass index status for A beta 42/40, p-tau217, GFAP, and NfL. However, these factors exhibited negligible or modest effects on A beta positivity on PET. DISCUSSIONOur findings highlight the importance of accurately interpreting plasma biomarkers for predicting A beta uptake in real-world settings. Highlights We investigated factor-Alzheimer's disease plasma biomarker associations in a large Korean cohort. Hemoglobin and estimated glomerular filtration rate affect the biomarkers independently of brain amyloid beta (A beta). Apolipoprotein E genotypes and body mass index status affect the biomarkers dependent on brain A beta. Addition of A beta-independent factors shows negligible effect in predicting A beta positivity. Adjusting for A beta-dependent factors shows a modest effect in predicting A beta positivity.

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