Correlations between plasma markers and brain Aβ deposition across the AD continuum: Evidence from SILCODE

Abstract

AbstractBACKGROUNDPrevious studies have found that Alzheimer's disease (AD)‐related plasma markers are associated with amyloid beta (Aβ) deposition, but the change of this association in different Aβ pathological stages remains unclear.METHODSData were obtained from the SILCODE. According to the standardized uptake value ratio (SUVR) and Aβ stage classification, correlation analysis was performed among plasma biomarkers, and voxel/SUVR values in the regions of interest (ROI) and clinical scale information, respectively. Mediation analysis was used to study the possible pathways.RESULTSThe proportion of cognitively normal (CN) and subjective cognitive decline (SCD) was the highest in stages A0 to 1, while in stages A2 to 4, the proportion of mild cognitive impairment (MCI) and AD increased. Plasma phosphorylated tau (p‐tau)181 and glial fibrillary acidic protein (GFAP) levels were significantly lower in stage A0 compared to the later phases. Two pathways demonstrated fully mediated effects: positron emission tomography (PET) SUVR–plasma p‐tau181–Mini‐Mental State Examination (MMSE) and PET SUVR–plasma GFAP–MMSE.DISCUSSIONThis study demonstrated the role of plasma biomarkers in the early stage of AD, especially in SCD, from both the clinical diagnosis and Aβ stage dimensions.Highlights Plasma ptau181 and GFAP level serve as indicators of early Alzheimer's disease and the pathologic Aβ staging classification. A possible ceiling effect of GFAP was observed in the mid‐to‐late stages of the AD course. This study confirms the role of AD plasma markers in promoting Aβ deposition at an early stage, particularly in females with subjective cognitive decline(SCD). The overlapping brain regions of plasma p‐tau181, GFAP, and neurofilament light for Aβ deposition in the brain in early AD were distributed across various regions, including the posterior cingulate gyrus, rectus gyrus, and inferior temporal gyrus.