The cross-talk between a-Synucleinopathies and T cell immunity in ADRD

Project Summary α-Synucleinopathies includes Dementia with Lewy Body (DLB), Parkinson's Disease with Dementia (PDD), and Alzheimer's Disease with Lewy Body Dementia (AD-LBD), that are highly associated with Alzheimer's Disease and Related Dementia (ADRD). The "Prion-like α-Syn Propagation" theory,

suggesting the GI tract as the origin of α-syn pathology and its subsequent spread to the brain, is a focal point of discussion. This cascade is implicated in neuroinflammation and cognitive decline, particularly in ADRD cases featuring α-syn pathology. Utilizing the established Gut-Brain α- synucleinopathy (GBAS) model, we aim to investigate the progression of these pathologies from the

gut to the brain, emphasizing the gut-brain axis's role in ADRD. Additionally, we shed light on the often- overlooked area of adaptive immunity, specifically T cell-mediated responses, noted for their diverse functions and immune potency, which may play a role in governing α-syn pathology, based on recent

research findings. Looking ahead, we explore the emerging potential of T-cell immunity in α-synuclein propagation within α-synucleinopathies. An interdisciplinary research team is poised to examine the impact of T-cell responses on α-syn pathology progression and explore potential applications of

immunotherapy. This collaborative effort aims to enrich our understanding of the complex mechanisms underlying neurodegenerative diseases and offer innovative therapeutic strategies for the future.