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Title: Brain-derived and circulating vesicle profiles indicate neurovascular unit dysfunction in early Alzheimer's disease
Authors: Gallart-Palau, Xavier
Serra, Aida
Hase, Yoshiki
Tan, Chee Fan
Chen, Christopher P.
Kalaria, Raj N.
Sze, Siu Kwan
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Gallart-Palau, X., Serra, A., Hase, Y., Tan, C. F., Chen, C. P., Kalaria, R. N. & Sze, S. K. (2019). Brain-derived and circulating vesicle profiles indicate neurovascular unit dysfunction in early Alzheimer's disease. Brain Pathology, 29(5), 593-605.
Project: NMRC-OF-IRG-0003-2016
Journal: Brain Pathology
Abstract: 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.
ISSN: 1015-6305
DOI: 10.1111/bpa.12699
Rights: © 2019 International Society of Neuropathology. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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