Objective: This study aims to stratify patients with Parkinson’s disease (PD) based on clinical features and several disease-associated biomarkers by analyzing the relationship between biomarkers, genes, amyloid PET (Positron Emission Tomography) and cognitive function.

Background: In Lewy Body Diseases (LBD), diagnosis and staging are defined by motor function and imaging. However, several factors are involved in the pathogenesis and aggregation of α-synuclein(α-syn) and PD is often associated with Alzheimer’s-related pathologies, such as amyloid-β(Aβ) and tau, in addition to α-syn pathology. Therefore, it is essential to analyze coexisting Alzheimer’s with α-syn pathology and background gene. In both PD and PDD/DLB, α-syn, Aβ, and tau aggregate in the prodromal phase. Biomarkers play essential roles in early diagnosis and staging to understand the biological status of neurodegenerative disorders.

Method: In this study, 36[文奥1] patients with clinically diagnosed with PD(n=13), PD with mild cognitive impairment (PD-MCI)(n=13) , and PDD/DLB(n=10), based on criteria, were enrolled, and each underwent testing for amyloid PET, α-syn seeds using Immuno Precipitation Real-Time Quaking-induced Conversion, Aβ1-40/1-42 ratio, pTau217, neurofilament light chain (NFL; a marker of neurodegeneration), Glial fibrillary acidic protein (GFAP; a maker of neuroinflammation), and ApoEε4 genes using blood tests were measured. The correlation between the presence of amyloid accumulation , differences in blood biomarker levels, clinical severity, and the rate of progression between PD, PD-MCI , and PDD/DLB was analyzed.

Results: Aβ1-40/1-42 and pTau217 showed a significant increase in the amyloid PET-positive group compared to the negative group. Aβ1-40/1-42 showed a significant increase in patients with APOE ε4 compared to those with APOE ε3. These suggest that amyloid deposition in the brain is reflected in the plasma and APOEε4 is a risk factor for amyloid deposition. In addition, a comparison of biomarkers among the three groups (PD, PD-MCI, and PDD/DLB) showed a significant increase in NFL in PDD/DLB compared to PD and PD-MCI. However, no significant differences were observed in Aβ1-40/1-42, pTau217, NFL, or GFAP.

Conclusion: We will increase the number of cases for further analysis and to elucidate the pathophysiology of coexisting amyloid pathology and synuclein pathology.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/stratification-study-of-alpha-synucleinopathy-by-body-fluid-biomarkers/