Contribution of clinical information to the predictive performance of plasma β-amyloid levels for amyloid positron emission tomography positivity

Background: Early detection of beta-amyloid (A beta) accumulation, a major biomarker for Alzheimer's disease (AD), has become important. As fluid biomarkers, the accuracy of cerebrospinal fluid (CSF) A beta for predicting A beta deposition on positron emission tomography (PET) has been extensively studied, and the development of plasma A beta is beginning to receive increased attention recently. In the present study, we aimed to determine whether APOE genotypes, age, and cognitive status increase the predictive performance of plasma A beta and CSF A beta levels for A beta PET positivity. Methods: We recruited 488 participants who underwent both plasma A beta and A beta PET studies (Cohort 1) and 217 participants who underwent both cerebrospinal fluid (CSF) A beta and A beta 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 A beta and CSF A beta, respectively, logistic regression and receiver operating characteristic analyses were performed. Results: When predicting A beta PET status, both plasma A beta 42/40 ratio and CSF A beta 42 showed high accuracy (plasma A beta area under the curve (AUC) 0.814; CSF A beta AUC 0.848). In the plasma A beta models, the AUC values were higher than plasma A beta 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 A beta models, when these variables were added. Conclusion: Plasma A beta might be a useful predictor of A beta deposition on PET status as much as CSF A beta, particularly when considered with clinical information such as APOE genotype and cognitive stage.

Automated summary

This study aimed to determine whether APOE genotypes, age, and cognitive status increase the predictive performance of plasma A beta and CSF A beta levels for A beta PET positivity. The results showed that both plasma A beta and CSF A beta can accurately predict A beta PET status, especially when considering clinical information such as APOE genotype and cognitive stage, plasma A beta has better predictive performance.