Proteomic profiling identifies serpin G1, ApoA-II, and LBP as potential biomarkers of dementia in an Egyptian cohort

Abstract

Background: Dementia, including Alzheimer's disease (AD), is a growing concern in Egypt, yet biomarker research in this population is scarce. Identifying serum biomarkers is essential for early diagnosis and understanding disease mechanisms in underrepresented groups.

Methods: We performed serum proteomic profiling on 20 Egyptian dementia patients and 10 cognitively unimpaired controls from the Egyptian Dementia Registry using mass spectrometry. Differential protein expression and pathway enrichment analyses were conducted.

Results: Of 260 quantified proteins, 21 were significantly different between dementia patients and controls (P < 0.05). Several serine protease inhibitor and immunoglobulin family proteins were downregulated, while apolipoprotein A-II was upregulated in dementia. Enrichment analysis revealed associations with inflammation, complement activation, and lipid metabolism pathways.

Conclusion: This is the first serum proteomic study of dementia in an Egyptian cohort, highlighting coordinated changes in protein families involved in inflammation and lipid metabolism, and emphasizing the importance of biomarker research in diverse populations.

Highlights: The study presents initial proteomic data from the Egyptian Dementia Registry.The Egyptian population has been underrepresented in the area of dementia research.Serine protease inhibitor G1, apolipoprotein A-II, and lipopolysaccharide binding protein emerged as significant proteins.The work lays the foundation for more understanding of molecular determinants in dementia in the Middle East.

Keywords: Alzheimer's disease; Egypt; biomarkers; dementia; proteomic profiling; underrepresented population.

FIGURE 1

Differentially expressed proteins in dementia using mass spectrometry quantification. A, PCA analysis of all proteins identified in the study cohorts (patients and controls). B, Volcano plot showing the difference in protein expression profiles between patients and controls. The plot shows the fold change in proteins NSAF (log2 [patient/control]) versus P value (−log10[P value]). Significantly expressed proteins are highlighted in red (upregulated) or blue (downregulated; P value < 0.05, and log2 fold change ≥ ± 0.5). C, Heatmap with hierarchical clustering of significantly expressed proteins across samples showing the altered pattern of expression between patients and controls. The relative expression of each protein is shown based on the z score of the protein's NSAF. D, Box plots show expression levels (NSAF) of the top significant proteins. E, Functional enrichment analysis with GO annotations of the 21 significant differentially expressed proteins (P value < 0.05) between patients and control. GO annotations, according to the biological process, molecular function, and cellular localization, are shown on the x axis, whereas the y axis represents the number of proteins. GO, Gene Ontology; NSAF, normalized spectral abundance factor; PCA, principal component analysis