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Peripheral and total circulating extracellular vesicle levels of advanced glycation end-products and RAGEs as possible biomarkers for mild cognitive impairment and Alzheimer's patients

Haddad, Mohamed, Perrotte, Morgane, ben Khedher,, Mohamed Raâfet, Fulop, Tamas et Ramassamy, Charles . Peripheral and total circulating extracellular vesicle levels of advanced glycation end-products and RAGEs as possible biomarkers for mild cognitive impairment and Alzheimer's patients In: Alzheimer’s Association International Conference (AACI), 27-31 July 2020, virtuel.

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Résumé

Background:Advanced glycation end-products (AGEs), their precursors methylglyoxal (MG), glyoxal (GO) and their receptors RAGEs are known to be involved in the pathophysiology of Alzheimer’s disease (AD). The aim of our study was to evidence the presence of RAGEs and glyoxalase-1 (GLO-1), the main enzyme involved in the degradation of MG, in the circulating extracellular vesicles (pEVs) from control subjects, mild cognitive impairment (MCI) and AD patients.

Method: EVs were isolated from plasma of control, MCI and AD subjects at different stages of the disease (early , moderate and severe). Their size, shape and density were characterized. The presence of EVs specific proteins TSG101, CD63, GAPDH were confirmed by Western Blot. MG and GO levels in serum were determined by HPLC. In addition, serum Pentosidine and CML levels were determined by competitive ELISA.

Result: Our data showed lower levels of RAGE in pEVs from MCI, early and moderate stage of AD patients as compared to the severe stage of AD patients. GLO-1 levels in pEVs were significantly decreased in early AD as compared to controls and MCI. Interestingly, RAGEs and GLO-1 levels in pEVs were correlated with the clinical cognitive scores. MG and GO levels in serum were higher in MCI and receiver-operating characteristic curves analysis showed that serum MG levels have higher sensitivity to differentiate MCI from controls but not from AD. Meanwhile, serum GO levels differentiate MCI from control and AD groups. The levels of CML in albumin-free serum proteins were higher in the early stage of AD while, the levels of pentosidine remained unchanged and were negatively correlated with the clinical cognitive scoresMMSE and MoCA. In contrast, the levels of N-(1-carboxymethyl)-L-lysine in pEVs were lower in the moderate stage of AD.

Conclusion: Levels of some AGEs and RAGEs in serum and in total circulating EVs could be used as possible biomarkers for MCI and AD. This work was supported by the Chaire Louise and André on Alzheimer’s disease, Foundation Armand-Frappier (CR) and CIHR grant (TF)

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique Alzheimer’s Dementia 2020;16(Suppl. 4):e044127 DOI: 10.1002/alz.044127
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 14 juill. 2021 15:40
Dernière modification: 14 juill. 2021 15:40
URI: https://espace.inrs.ca/id/eprint/11870

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