AUTHOR=Chun Min Young , Jang Hyemin , Kim Hee Jin , Kim Jun Pyo , Gallacher John , Allué José Antonio , Sarasa Leticia , Castillo Sergio , Pascual-Lucas María , Na Duk L. , Seo Sang Won , on behalf of DPUK TITLE=Contribution of clinical information to the predictive performance of plasma β-amyloid levels for amyloid positron emission tomography positivity JOURNAL=Frontiers in Aging Neuroscience VOLUME=15 YEAR=2023 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1126799 DOI=10.3389/fnagi.2023.1126799 ISSN=1663-4365 ABSTRACT=Background

Early detection of β-amyloid (Aβ) accumulation, a major biomarker for Alzheimer’s disease (AD), has become important. As fluid biomarkers, the accuracy of cerebrospinal fluid (CSF) Aβ for predicting Aβ deposition on positron emission tomography (PET) has been extensively studied, and the development of plasma Aβ 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 Aβ and CSF Aβ levels for Aβ PET positivity.

Methods

We 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.

Results

When 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.

Conclusion

Plasma Aβ might be a useful predictor of Aβ deposition on PET status as much as CSF Aβ, particularly when considered with clinical information such as APOE genotype and cognitive stage.