Integrated algorithm combining plasma biomarkers and cognitive assessments accurately predicts brain β-amyloid pathology.

Background: Accurate prediction of cerebral amyloidosis with easily available indicators is urgently needed for diagnosis and treatment of Alzheimer's disease (AD).

Methods: We examined plasma Aβ42, Aβ40, T-tau, P-tau181, and NfL, with APOE genotypes, cognitive test scores and key demographics in a large Chinese cohort (N = 609, aged 40 to 84 years) covering full AD spectrum. Data-driven integrated computational models were developed to predict brain β-amyloid (Aβ) pathology.

Results: Our computational models accurately predict brain Aβ positivity (area under the ROC curves (AUC) = 0.94). The results are validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Particularly, the models have the highest prediction power (AUC = 0.97) in mild cognitive impairment (MCI) participants. Three levels of models are designed with different accuracies and complexities. The model which only consists of plasma biomarkers can predict Aβ positivity in amnestic MCI (aMCI) patients with AUC = 0.89. Generally the models perform better in participants without comorbidities or family histories.

Conclusions: The innovative integrated models provide opportunity to assess Aβ pathology in a non-invasive and cost-effective way, which might facilitate AD-drug development, early screening, clinical diagnosis and prognosis evaluation.