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• W3022223417 abstract "Abstract Background The contributions of brain intercellular communication mechanisms, specifically extracellular vesicles (EV), to the progression of Alzheimer’s disease (AD) remain poorly understood. Methods Here, we investigated the role(s) of brain EV in the progressive course of AD through unbiased proteome-wide analyses of temporal lobe-derived EV and proteome-label quantitation of complementary remaining brain portions. Furthermore, relevant proteins identified were further screened by multiple reaction monitoring. Results Our data indicate that EV biogenesis was altered during preclinical AD with the genesis of a specific population of EV containing MHC class-type markers. The significant presence of the prion protein PrP was also manifested in these brain vesicles during preclinical AD. Similarly, sequestration of amyloid protein APP in brain EV coincided with the observed PrP patterns. In contrast, active incorporation of the mitophagy protein GABARAP in these brain vesicles was disrupted as AD progressed. Likewise, disrupted incorporation of LAMP1 in brain EV was evident from the initial manifestation of AD clinical symptoms, although the levels of the protein remained significantly upregulated in the temporal lobe of diseased brains. Conclusions Our findings indicate that impaired autophagy in preclinical AD coincides with the appearance of proinflammatory and neuropathological features in brain extracellular vesicles, facts that moderately remain throughout the entire AD progression. Thus, these data highlight the significance of brain EV in the establishment of AD neuropathology and represent a further leap toward therapeutic interventions with these vesicles in human dementias." @default.
• W3022223417 created "2020-05-13" @default.
• W3022223417 creator A5030301707 @default.
• W3022223417 creator A5040090793 @default.
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• W3022223417 date "2020-05-08" @default.
• W3022223417 modified "2023-10-17" @default.
• W3022223417 title "Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles" @default.
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• W3022223417 doi "https://doi.org/10.1186/s13195-020-00623-4" @default.
• W3022223417 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7210691" @default.
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• W3022223417 hasPublicationYear "2020" @default.
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