ben Khedher, Mohamed Raâfet; Haddad, Mohamed; Laurin, Danièle et Ramassamy, Charles 
ORCID: https://orcid.org/0000-0002-3252-5878
(2022).
Effect of APOE ε4 allele and redox signature in circulating extracellular vesicles in cognitively impaired patients converted to Alzheimer's disease
In: REDOX BIOLOGY CONGRESS 2022, August 24 - 26, 2022, Ghent, Belgique.
Résumé
Alzheimer’s disease (AD) is an age-related brain disorder and the leading cause of dementia. Oxidative stress is a unifying paradigm in the pathophysiology of AD and the presence of the apolipoprotein E4 variant (APOE ε4) is assumed to stimulate oxidative damage and enhance AD risk.
Exosomes or extracellular vesicles (EVs) (50-150 nm) are released by all cell types in the body. We have determined the impact of APOE ε4 on the level of apolipoproteins with antioxidant activities (apoE, apoJ, and apoD) along with oxidative markers in circulating extracellular vesicles (cEVs) and plasma from cognitively impaired-not demented (CIND) individuals converted to AD (CIND-AD).
Methods: EVs were isolated using the Total Exosome Isolation reagent and characterized according to the ISEV guidelines. Apolipoproteins E, J, and D and antioxidant response markers were determined in cEVs and plasma using immunoblotting, electrochemical examination, and spectrofluorimetry.
Results: We observed a significant decrease in the total antioxidant capacity (TAC) in the CIND-AD group. Levels of apoD in plasma and cEVs were higher in CIND-AD participants. Interestingly, protein carbonyls content and apoJ/D ratio were statistically different in cEVs but not in plasma from CIND-AD. Our data also indicate that TAC, cEVs protein carbonyls, cEVs apoJ/D levels were correlated with the neurocognitive Mini-Mental State Exam (MMSE) scores and are APOE ε4-dependant.
Discussion: Our results demonstrate that cEVs redox signature is more relevant than plasma for reflecting specific brain and systemic changes in early AD onset and particularly in APOE ε4 carriers.
Conclusion: Our findings support the pathological redox linkage between APOE ε4 and AD onset and suggest the use of cEVs oxidative signature in early AD diagnosis.
| Type de document: | Document issu d'une conférence ou d'un atelier |
|---|---|
| Informations complémentaires: | Free Radical Biology and Medicine 189: pp.11 |
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 04 janv. 2024 07:57 |
| Dernière modification: | 04 janv. 2024 07:57 |
| URI: | https://espace.inrs.ca/id/eprint/13343 |
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