Plasma proteomics profiling reveals differential protein expression in Alzheimer's and frontotemporal dementia
Photo by National Institute of Allergy and Infectious Diseases / Unsplash
Key Takeaway
Consider plasma proteomics signatures as preliminary targets for dementia diagnosis in Asian cohorts.
This observational cohort study analyzed plasma proteomics profiling using Olink Explore-HT in an Asian cohort of 101 individuals with known pTau217 status, focusing on Alzheimer's disease and frontotemporal dementia. The primary outcome was differential protein expression, with no comparator reported and follow-up duration not reported. Main results showed 1,168 proteins differentially expressed in Alzheimer's disease and 370 in frontotemporal dementia, both with FDR<0.05, along with distinct and overlapping proteomic signatures reflecting gliosis, synaptic dysfunction, immune activation, and metabolic pathways. Prioritized proteins correlated with cognitive performance and plasma phosphorylated tau, Aβ42, and neurofilament light chain, with strong concordance in cross-platform validation against large independent datasets. Safety and tolerability data were not reported. Key limitations include the cohort being limited to Asian individuals and reliance on plasma proteomics without tissue validation. The findings support a scalable framework for blood-based biologically informed targets for precision diagnosis and therapeutic stratification, but as associations from an observational study, they do not infer causation and have uncertain generalizability beyond this cohort.
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View Original Abstract ↓
INTRODUCTION: Alzheimer's disease (AD) and frontotemporal dementia (FTD) have considerable clinical and pathological overlap. While plasma proteomics has advanced in AD, deep comparative analyses with FTD-particularly in diverse, biomarker-confirmed Asian cohorts-remain limited. METHODS: Plasma from 101 individuals with known pTau217 status was profiled using Olink Explore-HT. Differential expression-pathway enrichment, penalized regression-GLMNET, single-cell transcriptomic integration, associations with cognitive measures and, cross-platform validation were performed. RESULTS: Among 5,400-proteins, 1,168 were differentially expressed in AD and 370 in FTD (FDR<0.05). Distinct and overlapping proteomic signatures were identified in AD and FTD, reflecting gliosis, synaptic dysfunction, immune activation, and metabolic pathways. Prioritized proteins correlated with cognitive performance and plasma phosphorylated tau, A{beta}42, and neurofilament light chain, linking circulating proteins to disease severity. Cross platform validation revealed strong concordance with large independent datasets. CONCLUSION: Comprehensive plasma proteomics in Asian cohort supports scalable framework for blood-based biologically informed targets for precision diagnosis and therapeutic stratification.
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