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Specific signatures of circulating extracellular vesicles emerged as novel biological tools for the detection of biomarkers for MCI and Alzheimer’s disease

Ramassamy, Charles . Specific signatures of circulating extracellular vesicles emerged as novel biological tools for the detection of biomarkers for MCI and Alzheimer’s disease In: Alzheimer’s Association International Conference (AACI), 27-31 July 2020, virtuel.

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Background: Alzheimer’s disease (AD) is characterized by a series of overlapping pathophysiological cascades, including the aggregation of β-amyloid plaques and the formation of neurofibrillary tangles derived from hyperphosphorylated tau proteins. Actually, the search for peripheral biomarkers for AD that reflect AD-related processes in the brain has received considerable attention but the clinical utility of blood-based biomarkers is not validated. Accumulating evidence supports the central role of exosomes or extracellular vesicles (EVs) in the pathophysiology of AD. In the brain, they can act as vehicles for the cell-to-cell transfer of the AD pathogenic proteins. Our objectives were to demonstrate that some proteins cargo in the circulating EVs represent a great potential in harbor disease-specific molecular signatures of brain disorders, making them an ideal source of biomarkers.

Method: We have isolated EVs from plasma (pEVs) of control, MCI and AD subjects at different stages of the disease (mild, moderate, severe). Then, their size, shape and density were characterized by transmission electronic microscopy and nanoparticles tracking analysis (NTA). The presence of pEVs specific proteins TSG101, CD63, GAPDH were confirmed by Western Blot and AD-related proteins were quantified by Luminex assay.

Result: Our data showed that the levels of these proteins were higher in pEVs than in plasma indicating that the pEVs represent a sensitive tool to screen peripheral biomarkers. We observed a reduction of tTau in pEVs from MCI subjects while the APP concentration was reduced in pEVs from MCI and early AD. Interestingly, pTauT181 and APP concentrations in pEVs were correlated with cognitive performances (MMSE , MoCA). Aβ42 and pTau-T181 levels in pEVs were unchanged in MCI but elevated in moderate AD patients compared to controls. Abnormal levels of APP an pTau-T181/tTau ratio in pEVs levels demonstrated good accuracy to define MCI and AD staging.

Conclusion: Taken together, these results demonstrated that the identification of these proteins in pEVs could have great implication in differentiating MCI individuals to AD patients and to monitor the disease progression. 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):e041215 DOI: 10.1002/alz.041215
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/11869

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