Amyloid‐beta misfolding and GFAP predict risk of clinical Alzheimer's disease diagnosis within 17 years

Abstract Introduction Blood‐based biomarkers for Alzheimer's disease (AD) are urgently needed. Here, four plasma biomarkers were measured at baseline in a community‐based cohort followed over 17 years, and the association with clinical AD risk was determined. Methods Amyloid beta (Aβ) misfolding status as a structure‐based biomarker as well as phosphorylated tau 181 (P‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) concentration levels were determined at baseline in heparin plasma from 68 participants who were diagnosed with AD and 240 controls without dementia diagnosis throughout follow‐up. Results Aβ misfolding exhibited high disease prediction accuracy of AD diagnosis within 17 years. Among the concentration markers, GFAP showed the best performance, followed by NfL and P‐tau181. The combination of Aβ misfolding and GFAP increased the accuracy. Discussion Aβ misfolding and GFAP showed a strong ability to predict clinical AD risk and may be important early AD risk markers. Aβ misfolding illustrated its potential as a prescreening tool for AD risk stratification in older adults.