Biomarkers enable earlier Parkinson’s Disease (PD) detection, improving diagnosis and treatment. A major pathological hallmark of PD is the accumulation of Lewy Bodies composed of misfolded a- Synuclein (aSyn). How aSyn brain pathology in the central nervous system (CNS) might be caused by pathogens entering the Enteric Nervous System (ENS)—a “gut-to-brain axis”—is still not properly understood. Plasma apolipoprotein A1 (ApoA1) is a biomarker that associates with PD risk and severity, and evidence has shown that ApoA1 directly interacts with aSyn. This study will aim to evaluate how the presence or lack of ApoA1 under conditions of intestinal inflammation could affect the pathological spread of aSyn from the gut to brain in vivo. Specifically, the study tests how treating colitis-induced ApoA1 wildtype (WT) and knockout (KO) mice with aSyn Preformed Fibrils (PFF) or monomers affects gut and brain pathology.