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Brain-derived and circulating vesicle profiles indicate neurovascular unit dysfunction in early Alzheimer’s disease

Lookup NU author(s): Dr Yoshiki Hase, Professor Raj Kalaria

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Abstract

© 2019 International Society of Neuropathology Vascular factors that reduce blood flow to the brain are involved in apparition and progression of dementia. We hypothesized that cerebral hypoperfusion (CH) might alter the molecular compositions of brain intercellular communication mechanisms while affecting the neurovascular unit in preclinical and clinical human dementias. To test that hypothesis, mice were subjected to bilateral common carotid stenosis (BCAS) and the molecular compositions of brain-derived and circulating extracellular vesicles (EVs) were assessed. Murine brain vesicle profiles were then analyzed in parallel with brain EVs from post-mortem subjects affected by preclinical Alzheimer’s Disease (AD) and mixed dementias. Brain EVs were identified with molecular mediators of hypoxia responses, neuroprotection and neurotoxicity in BCAS mice, patterns also partially resembled by subjects with preclinical AD and mixed dementias. Together these findings indicate that brain EVs represent a promising source of therapeutic targets and circulating markers of neurovascular insult in idiopathic dementias. Furthermore, the results obtained generate novel and compelling hypotheses about the molecular involvement of the vascular component in the etiology of human dementias.


Publication metadata

Author(s): Gallart-Palau X, Serra A, Hase Y, Tan CF, Chen CP, Kalaria RN, Sze SK

Publication type: Article

Publication status: Published

Journal: Brain Pathology

Year: 2019

Pages: Epub ahead of print

Online publication date: 10/01/2019

Acceptance date: 20/12/2018

ISSN (print): 1015-6305

ISSN (electronic): 1750-3639

Publisher: Wiley-Blackwell Publishing, Inc.

URL: https://doi.org/10.1111/bpa.12699

DOI: 10.1111/bpa.12699


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