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

Lookup NU author(s): Professor Johannes AttemsORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.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 glutathione S-transferase omega 1 (GSTO1) levels linked to single nucleotide polymorphism (SNP) rs4925 and increased superoxide dismutase 1 (SOD1) levels in AD. Bioinformatics revealed copper chaperone for superoxide dismutase (CCS) and glutathione peroxidase 1 (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. Highlights: Platelets mirror several Alzheimer's disease (AD)–dependent neuronal changes, valuable for blood tests. As a start, 60 AD-associated frontal lobe proteins were identified by top-down proteomics. Fifty percent of these 60 AD-affected brain proteins are represented identically in platelets. Among these, glutathione S-transferase omega 1 (GSTO1), superoxide dismutase 1 (SOD1), copper chaperone for superoxide dismutase (CCS), and glutathione peroxidase 1 (GPX1) are identically AD related in brain and platelets. SOD1 and its crucial activating partner CCS are altered in the platelets of patients with mild cognitive impairment.

Publication metadata

Author(s): Ercan H, Reumiller CM, Muhlberger J, Hsu F, Schmidt GJ, Umlauf E, Miller I, Rappold E, Attems J, Oehler R, Zellner M

Publication type: Article

Publication status: Published

Journal: Alzheimer's and Dementia

Year: 2025

Volume: 21

Issue: 4

Print publication date: 01/04/2025

Online publication date: 06/04/2025

Acceptance date: 02/12/2024

Date deposited: 23/04/2025

ISSN (print): 1552-5260

ISSN (electronic): 1552-5279

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/alz.70117

DOI: 10.1002/alz.70117

Data Access Statement: The proteomics raw data of this study are available in Mendeley Data at (https://data.mendeley.com/datasets/kjhsnpff5k/1).

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