Plasma Proteome Profiling Identified Biomarkers for the Differential Diagnosis and Molecular Staging of Neurodegenerative Dementias

Blood-based biomarkers are emerging as scalable tools for the diagnosis and monitoring of neurodegenerative diseases. However, markers enabling differential diagnosis across major dementias remain limited. A recent study aimed to address this gap by analyzing 1,318 plasma samples from well-characterized international cohorts using large-scale plasma proteomics. The researchers identified more than 200 dysregulated proteins across disease groups, providing valuable insights into the molecular mechanisms underlying neurodegenerative diseases. Glial fibrillary acidic protein (GFAP) was found to be strongly increased along the Alzheimer’s disease continuum, while integrin alpha-V and integrin alpha-M were consistently reduced in Lewy body disorders, including autopsy-confirmed cases. In contrast, elevated neurofilament light chain and lower GFAP levels were associated with frontotemporal dementia. These findings suggest that plasma proteomics can be a valuable approach for biomarker-based differential diagnosis and disease staging across major neurodegenerative dementias. Furthermore, the researchers developed a 21-protein quantitative multiplex panel based on their findings, which was validated in an independent multicenter cohort (n = 805). The validation results supported the utility of this panel as a diagnostic tool for distinguishing between Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia. However, it is essential to note that these findings are based on research-use-only laboratory peptides and should not be used for clinical diagnosis or treatment without further validation in a clinical setting.