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Prior investigations have elucidated pathophysiological interactions involving blood coagulation and neurodegenerative diseases. These interactions pertain to age-related effects and a mild platelet antiaggregant function of exogenous α-Synuclein. Our study sought to explore whether cerebrospinal fluid (CSF) levels of tissue factor (TF), the initiator of the extrinsic pathway of hemostasis, differ between controls (CON) compared to patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), considering that these conditions represent a spectrum of α-Synuclein pathology. We further investigated whether TF levels are associated with longitudinal progression in PD. We examined CSF levels of TF in 479 PD patients, 67 patients diagnosed with DLB, and 16 CON in order to evaluate potential continuum patterns among DLB, PD, and CON. Of the 479 PD patients, 96 carried a GBA1variant (PD GBA1), while the 383 non-carriers were classified as PD wildtype (PD WT). We considered both longitudinal clinical data as well as CSF measurements of common neurodegenerative markers (amyloid-β 1-42, h-Tau, p-Tau, NfL, α-Synuclein). Kaplan-Meier survival and Cox regression analysis stratified by TF tertile levels was conducted. Higher CSF levels of TF were associated with an older age at examination in PD and a significant later onset of postural instability in PD GBA1. TF levels were lower in male vs. female PD. DLB GBA1exhibited the lowest TF levels, followed by PD GBA1, with CON showing the highest levels. TF as representative of blood hemostasis could be an interesting CSF candidate to further explore in PD and DLB. Parkinson’s disease is a common age-related condition, primarily affecting older individuals. However, it shows a wide range of symptoms and clinical courses, influenced by genetic mutations, neuroinflammatory processes and lifestyle factors. Research into the disease’s mechanisms is important for developing new therapies that could potentially slow its progression. Early diagnosis is also essential, as new disease-modifying therapies are most effective when started at an early stage of the disease. In this paper, we focus on a protein called tissue factor, which plays a role in both blood coagulation and neuroinflammation. Proteins involved in blood-coagulation also exhibit an increase in blood-concentration with higher age. Also, a subtle platelet antiaggregant function of exogenous α-Synuclein was found, a protein which aggregates in the brain of patients with Parkinson’s disease. Additionally, higher tissue factor levels were found in plaques of proteins (amyloid-β 1-42) found in Alzheimer’s disease. Thus, tissue factor could be a promising biomarker candidate for neurodegenerative diseases. We analyzed the concentration of this protein in the cerebrospinal fluid of 479 patients with Parkinson’s disease, 16 control participants, and 67 patients with dementia with Lewy bodies, a sub-type of Parkinson’s disease with exceptionally high levels of α-Synuclein in the brain. Our findings showed the lowest levels of tissue factor in patients with dementia with Lewy bodies, followed by those with typical Parkinson’s disease, and the highest levels in controls. Additionally, older patients had higher tissue factor levels than younger patients, and levels were lower in male patients compared to female patients. Thus, measuring tissue factor levels could help in diagnosing Parkinson’s disease. Further studies, especially with larger control groups, are needed to confirm these results. Additionally, exploring the connections between blood coagulation and Parkinson’s disease could improve our understanding of the disease’s mechanisms, potentially leading to new pharmaceutical developments.