Researchers have identified a biomarker in cerebrospinal fluid (CSF) that shows promise in distinguishing between different forms of dementia, including Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). The biomarker, detected via assays measuring DDC (dopamine-dependent component), could aid in earlier and more accurate diagnoses, according to a study involving data from over 1,500 participants across six international cohorts.
The study, which utilized both in-house developed immunoassays and existing technologies, analyzed CSF samples from individuals with AD, DLB, Parkinson’s disease (PD), mild cognitive impairment (MCI), and healthy controls. Researchers found that DDC levels were significantly elevated in patients with DLB compared to those with AD, PD, or MCI. The findings, published in Nature Communications, suggest DDC could serve as a valuable tool for differentiating between these neurodegenerative diseases, which often present with overlapping symptoms.
The research involved a multi-center approach, incorporating data from cohorts in the Netherlands, Italy, Denmark, the United States, and South Korea. Participants underwent standard neurological and cognitive assessments, and diagnoses were made according to established international criteria. AD diagnoses were supported by measurements of Aβ42 and pTau in CSF, while DaT-PET imaging was used to assess dopamine transporter function, particularly in differentiating DLB from other conditions.
“Accurate diagnosis is crucial for appropriate patient management and clinical trial enrollment,” explained researchers from the University of Perugia, Italy, who were involved in the study. “Currently, differentiating between DLB and AD can be challenging, leading to delays in treatment and potentially inappropriate care.”
The study too investigated the relationship between DDC levels and clinical features of DLB, such as visual hallucinations and fluctuations in alertness. Higher DDC levels were associated with the presence of these core DLB symptoms. Researchers found a correlation between CSF DDC levels and abnormalities observed on DaT-PET scans, which are indicative of dopamine neuron loss.
The development of the immunoassays used in the study was performed on the SimplePlex Ella and Quanterix Simoa platforms, with rigorous analytical validation to ensure accuracy and reliability. Researchers performed a Passing Bablok regression to account for differences between Ella V4 and V5 cartridge formats, ensuring comparability of data across cohorts.
While the findings are promising, researchers caution that further validation is needed in larger, independent cohorts. The World Medical Association’s Declaration of Helsinki, most recently revised in October 2024, guided the ethical conduct of the research, ensuring informed consent from all participants and approval from local ethical committees. The Declaration of Helsinki emphasizes the importance of protecting the rights and well-being of research participants, a principle central to this study.
The study’s findings build upon previous research exploring the role of α-synuclein pathology in DLB. α-synuclein is a protein that accumulates in the brains of individuals with Parkinson’s disease and DLB, forming Lewy bodies. The researchers suggest that DDC may reflect the extent of α-synuclein pathology and its impact on dopamine neuron function. Further research is planned to investigate the relationship between DDC levels and other biomarkers of neurodegeneration.
