Plasma oligomeric amyloid‐β and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease

Abstract

AbstractBackgroundThe amyloid hypothesis linking amyloid β protein (Aβ) to Alzheimer’s disease (AD) is the key pathological event. It has shifted in recent years to suggest Oligomeric Amyloid‐β (OAβ) as a promising candidate for AD diagnosis. We aimed to depict the plasma levels of OAβ across a spectrum of cognitive stages and to explore the correlation between OAβ and specific cognitive domains.MethodIn this single‐center observational study, we included 494 individuals who had normal cognition (NC), mild cognitive impairment (MCI), and AD. Cognitive function was assessed across four cognitive domains (language and related functions, visuospatial functions, memory, and frontal/executive functions) and with the Mini‐Mental State Examination (MMSE). Participants were defined as: 1) NC with a percentile >16th in all sub‐tests of the SNSB‐C, 2) MCI with a percentile >16th in one or more sub‐tests of the SNSB‐C and K‐IADL < 0.43, and 3) AD with a percentile >16th in one or more sub‐tests of the SNSB‐C and K‐IADL ≥ 0.43. The MDS‐AD assay kit (PeopleBio Inc., Gyeonggi‐do, Republic of Korea) was used to quantify the levels of OAβ in the plasma.ResultThe plasma OAβ levels gradually increased among different cognitive stages of AD, with the lowest concentration in the NC (0.72 ng/ml), an increase in the MCI (0.76 ng/ml), and the highest concentration in AD (1.08 ng/ml). The plasma OAβ levels were significantly correlated with MMSE scores (r = ‐0.119, P‐value = 0.0083), the Korean‐Boston Naming Test (r = ‐0.090, P‐value = 0.0464), and the Trail Making Test‐Elderly (TMT‐E) (r = ‐0.146, P‐value = 0.0012). After adjusting for confounding variables, the elevated plasma OAβ were associated with worse performance on MMSE (Adjusted beta = ‐0.691; SE = 0.27, P‐value = 0.0100) and TMT‐E (Adjusted beta = ‐7.721; SE = 2.33, P‐value = 0.0100) as frontal/executive functions.ConclusionPlasma OAβ has correlated with language and related functions and frontal/executive functions, suggesting its potential biomarker for clinical manifestations of AD.