Contribution of clinical information to the predictive performance of plasma Aβ levels for Aβ PET positivity

Abstract

AbstractBackgroundEarly detection of β‐amyloid (Aβ) accumulation, a major biomarker for Alzheimer’s disease (AD), has become important. While Aβ deposition can be detected by positron emission tomography (PET), practical fluid Aβ biomarker is also being developed recently. In the present study, we aimed to determine whether APOE genotypes, age, and cognitive status increase the predictive performance of fluid Aβ levels for amyloid PET positivity.MethodsWe recruited 488 participants who underwent both plasma Aβ and Aβ PET studies (Cohort 1) and 217 participants who underwent both cerebrospinal fluid (CSF) Aβ and Aβ PET studies (Cohort 2). Plasma and CSF samples were analyzed using ABtest‐MS, an antibody‐free liquid chromatography‐differential mobility spectrometry‐triple quadrupole mass spectrometry method and INNOTEST enzyme‐linked immunosorbent assay kits, respectively. To evaluate the predictive performance of plasma Aβ and CSF Aβ, respectively, logistic regression and receiver operating characteristic analyses were performed.ResultsWhen predicting Aβ PET status, both plasma Aβ42/40 ratio and CSF Aβ42 showed high accuracy (plasma Aβ area under the curve (AUC) 0.814; CSF Aβ AUC 0.848). In the plasma Aβ models, the AUC values were higher than plasma Aβ alone model, when the models were combined with either cognitive stage (p < 0.001) or APOE genotype (p = 0.011). On the other hand, there was no difference between the CSF Aβ models, when these variables were added.ConclusionsPlasma Aβ might be a useful predictor of Aβ PET status as much as CSF Aβ, particularly when considered with clinical information.