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Small RNA fingerprinting of Alzheimer’s disease frontal cortex extracellular vesiclesand their comparison with peripheral extracellular vesicles

journal contribution
posted on 18.01.2021, 03:44 by Lesley Sim, LJ Vella, KJ Barnham, C McLean, CL Masters, Andrew Hill
© 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. Alzheimer’s disease is a progressive neurodegenerative disorder, with the strongest disease-associated changes observed at clinical or end-stage disease. Transcriptomic deregulation of miRNA expression can spread via “horizontal” RNA transfer through extracellular vesicles (EVs) to act in conjunction with proteins, leading to changes in mRNA, which can provide early signals to indicate forthcoming neuropathological changes in the brain. Here, we analysed the small RNA content, in particular, miRNA, contained in brain-derived EVs isolated from the frontal cortex of Alzheimer’s subjects (n = 8) and neurological control subjects (n = 9). Brain-derived EVs were found to contain an upregulation of disease-associated miRNA. RNA species from brain-derived EVs were correlated with miRNA profiles obtained from matching total brain homogenate. These results provide a blueprint into the biological pathways potentially effected during disease that may be assisted by brain-derived EV RNA horizontal transfer.We also correlated the miRNA changes in the brain with those detected in peripheral EVs collected from serum of Alzheimer’s disease patients (n = 23, and healthy controls, n = 23) and revealed a panel of miRNA that could be used as a liquid brain biopsy. Overall, our study provides the first interrogation of the small RNA contents in brain-derived EVs and how they could be used to understand the early pathological changes in Alzheimer’s disease which will benefit the development of an early diagnostic blood test.

Funding

This work was supported by the National Health and Medical Research Council [GNT1041413 to AFH; GNT1132604 to AFH, CLM and KJB] and the Dementia Collaborative Research Centre Research Grant [AFH and LC]. The collection and processing of the brain tissue which has been used for multiple projects was funded by the Mason Foundation awarded to Andrew Watt and Kevin J. Barnham; Dementia Collaborative Research Centres, Australia.

History

Publication Date

01/01/2020

Journal

Journal of Extracellular Vesicles

Volume

9

Issue

1

Article Number

1766822

Pagination

15p. (p. 1-15)

Publisher

Taylor & Francis

ISSN

2001-3078

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

Licence

Exports