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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2020

01-12-2020 | Alzheimer's Disease | Research

Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles

Authors: Xavier Gallart-Palau, Xue Guo, Aida Serra, Siu Kwan Sze

Published in: Alzheimer's Research & Therapy | Issue 1/2020

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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.
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Metadata
Title
Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles
Authors
Xavier Gallart-Palau
Xue Guo
Aida Serra
Siu Kwan Sze
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2020
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-020-00623-4

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