Platelets reflect changes in the frontal lobe antioxidant system in Alzheimer's disease

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INTRODUCTION: Blood biomarkers reflecting Alzheimer’s disease (AD) pathophysiology can improve diagnosis and treatment. METHODS: We applied top-down proteomics to compare frontal lobe from 17 AD cases and 11 controls to blood platelets from a second independent study group of 124 AD patients, 61 with mild cognitive impairment (MCI), and 168 controls. Findings were immunologically validated. RESULTS: Sixty AD-associated proteoforms were identified in frontal lobe, with 26 identically represented in platelets. Validation in platelet samples confirmed elevated GSTO1 levels linked to SNP rs4925 and increased SOD1 levels in AD. Bioinformatics revealed CCS and GPX1 as integral partners of these antioxidant enzymes. Both were detected to be reduced in frontal lobes and platelets in AD. SOD1 and CCS are already changed in MCI. DISCUSSION: These four novel blood biomarkers, integrated with traditional AD biomarkers, may facilitate patient risk assessment and treatment, with SOD1 and CCS alterations in MCI offering early diagnostic potential.

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