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

Huriye Ercan; Christina Maria Reumiller; Jacqueline Mühlberger; Felicia Hsu; Georg Johannes Schmidt; Ellen Umlauf; Ingrid Miller; Eduard Rappold; Johannes Attems; Rudolf Oehler; Maria Zellner

doi:10.1002/alz.70117

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Title (eng)

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

Author

Huriye Ercan

Christina Maria Reumiller

Jacqueline Mühlberger

Felicia Hsu

Georg Johannes Schmidt

Ellen Umlauf

Ingrid Miller

University of Veterinary Medicine Vienna

Eduard Rappold

Johannes Attems

Rudolf Oehler

Maria Zellner

Abstract (eng)

Blood biomarkers reflecting Alzheimer's disease (AD) pathophysiology can improve diagnosis and treatment.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.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.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.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.

Keywords (eng)

HumansAlzheimer Disease BloodAlzheimer Disease GeneticsAlzheimer Disease PathologyAlzheimer Disease MetabolismBlood Platelets MetabolismMaleFemaleFrontal Lobe MetabolismAgedSuperoxide Dismutase-1 MetabolismBiomarkers BloodCognitive Dysfunction BloodCognitive Dysfunction MetabolismGlutathione Peroxidase MetabolismGlutathione Peroxidase BloodGlutathione Peroxidase GPX1ProteomicsSuperoxide Dismutase MetabolismAged, 80 and overGlutathione Transferase MetabolismPolymorphism, Single Nucleotide GeneticsAntioxidants Metabolism

Type (eng)

journal article

Language

[eng]

Persistent identifier

https://phaidra.vetmeduni.ac.at/o:4077

DOI

10.1002/alz.70117

Is in series

Title (eng)

Alzheimers & Dementia

Volume