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Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes

Nortley, R; Korte, N; Izquierdo, P; Hirunpattarasilp, C; Mishra, A; Jaunmuktane, Z; Kyrargyri, V; ... Attwell, D; + view all (2019) Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes. Science , 365 (6450) , Article 250. 10.1126/science.aav9518. Green open access

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Abstract

Cerebral blood flow is reduced early in Alzheimer’s disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. Here we used live and rapidly-fixed biopsied human tissue to establish disease-relevance, and rodent experiments to define mechanism. We found that, in humans with cognitive decline, amyloid β (Aβ) constricts brain capillaries at pericyte locations. This was caused by Aβ generating reactive oxygen species, which evoked the release of endothelin-1 (ET) that activated pericyte ETA receptors. Capillary, but not arteriole, constriction also occurred in vivo in a mouse model of AD. Thus, inhibiting the capillary constriction caused by Aβ could potentially reduce energy lack and neurodegeneration in AD.

Type: Article
Title: Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.aav9518
Publisher version: https://doi.org/10.1126/science.aav9518
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10077413
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