Background: Accumulating evidence has shown that a-synuclein (a-syn) pathology is involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to investigate the association between the levels of plasma a-syn protein, urinary Alzheimer-associated neuronal thread protein (AD7c-NTP), apolipoprotein epsilon 4 (ApoE e4) alleles and cognitive decline in 60 AD patients compared with 28 age-matched normal controls (NCs) at a sin-gle center. Material/Methods: All participants underwent a-syn, apolipoprotein E (ApoE), AD7c-NTP, cholesterol (CHO), high-density lipopro-tein (HDL), low-density lipoprotein (LDL) and triglycerides (TGs) analyses, neuropsychological scale assessments and neuroimaging analysis. Moreover, urine and peripheral blood samples were collected from all participants. The levels of plasma a-syn and AD7c-NTP were assayed using an enzyme-linked immunosorbent assay (ELISA) kit. Other test results were obtained from China-Japan Friendship Hospital. Results: We found that plasma a-syn levels were significantly different between AD patients and NCs (p=0.045). a-Syn levels were also associated with AD7c-NTP (r=0.231, p=0.03) but not ApoE e4 (Z=-0.147, p=0.883) levels. Neither a-syn [CHO (p=0.432), HDL (p=0.484), LDL (p=0.733) or TGs (p=0.253)] nor AD7c-NTP [CHO (p=0.867), HDL (p=0.13), LDL (p=0.57) or TGs (p=0.678)] had a relationship with lipids. Conclusions: This study showed that the levels of plasma a-syn protein and urinary AD7c-NTP were significantly increased in AD patients compared with NCs, but not with ApoE alleles or serum lipid levels.