Abstract
OBJECTIVE: Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common neurodegenerative diseases with distinct but overlapping pathogenic mechanisms. The clinical similarities between these diseases often result in high misdiagnosis rates, leading to serious consequences. Peripheral blood mononuclear cells (PBMCs) are easy to collect and can accurately reflect the immune characteristics of both DLB and AD. METHODS: We utilized time-of-flight mass cytometry (CyTOF) with single-cell resolution to quantitatively analyze peripheral PBMCs, identifying 1228 immune characteristics. Based on the top-selected immune features, we constructed immunological elastic net (iEN) models. RESULTS: These models demonstrated high diagnostic efficacy in distinguishing diseased samples from healthy donors as well as distinguishing AD and DLB cases. The selected features reveal that the primary peripheral immune characteristic of AD is a decrease in total T cells, while DLB is characterized by low expression of I-kappa-B-alpha (IKBα) in the classical monocyte subset. CONCLUSIONS: These findings suggest that peripheral immune characteristics could serve as potential biomarkers, facilitating the diagnosis of neurodegenerative diseases.