Proximity-extension dementia-panel in 41 brain disorders: a meta-analysis

<title>Abstract</title> <p> Fluid biomarkers detectable in cerebrospinal fluid (CSF) and blood offer critical insights into neurodegenerative disorders ^1-5 , such as Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies ^6-9 . Previous proximity-extension assay (PEA) studies have discovered 42 CSF biomarkers for distinguishing the aforementioned dementias ^6-9 ; however, their disease- and matrix-specificity remain understudied. We developed and employed a federated meta-analysis framework to explore these biomarkers by analysing results from 65 case-control cohorts, including 20,576 samples (CSF n = 8,766, blood n = 11,810) covering 41 neurological and psychiatric conditions. Our comprehensive analysis identified both distinct and shared patterns of protein alterations across the spectrum of brain disorders, with marked differences observed between CSF and blood profiles. While several biomarkers demonstrated significant changes within their primary disease contexts, we also observed convergent dysregulation of proteins related to neuroinflammation and tau pathology across multiple conditions. These findings highlight the importance of fluid-specific biomarker assessment and provide a resource to inform the development and contextualization of novel biomarkers for brain disorders. </p>