Amyloid β oligomers constrict human capillaries in alzheimer’s disease via signaling to pericytes

Ross Nortley, Nils Korte, Pablo Izquierdo, Chanawee Hirunpattarasilp, Anusha Mishra, Zane Jaunmuktane, Vasiliki Kyrargyri, Thomas Pfeiffer, Lila Khennouf, Christian Madry, Hui Gong, Angela Richard-Loendt, Wenhui Huang, Takashi Saito, Takaomi C. Saido, Sebastian Brandner, Huma Sethi, David Attwell

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalScience
DOIs
StatePublished - Jan 1 2019

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Pericytes
Amyloid
Alzheimer Disease
Constriction
Cerebrovascular Circulation
Rodent Diseases
Brain
Arterioles
Endothelin-1
Vascular Resistance
Reactive Oxygen Species

ASJC Scopus subject areas

  • General

Cite this

Nortley, R., Korte, N., Izquierdo, P., Hirunpattarasilp, C., Mishra, A., Jaunmuktane, Z., ... Attwell, D. (2019). Amyloid β oligomers constrict human capillaries in alzheimer’s disease via signaling to pericytes. Science. https://doi.org/10.1126/science.aav9518

Amyloid β oligomers constrict human capillaries in alzheimer’s disease via signaling to pericytes. / Nortley, Ross; Korte, Nils; Izquierdo, Pablo; Hirunpattarasilp, Chanawee; Mishra, Anusha; Jaunmuktane, Zane; Kyrargyri, Vasiliki; Pfeiffer, Thomas; Khennouf, Lila; Madry, Christian; Gong, Hui; Richard-Loendt, Angela; Huang, Wenhui; Saito, Takashi; Saido, Takaomi C.; Brandner, Sebastian; Sethi, Huma; Attwell, David.

In: Science, 01.01.2019.

Research output: Contribution to journalArticle

Nortley, R, Korte, N, Izquierdo, P, Hirunpattarasilp, C, Mishra, A, Jaunmuktane, Z, Kyrargyri, V, Pfeiffer, T, Khennouf, L, Madry, C, Gong, H, Richard-Loendt, A, Huang, W, Saito, T, Saido, TC, Brandner, S, Sethi, H & Attwell, D 2019, 'Amyloid β oligomers constrict human capillaries in alzheimer’s disease via signaling to pericytes', Science. https://doi.org/10.1126/science.aav9518
Nortley, Ross ; Korte, Nils ; Izquierdo, Pablo ; Hirunpattarasilp, Chanawee ; Mishra, Anusha ; Jaunmuktane, Zane ; Kyrargyri, Vasiliki ; Pfeiffer, Thomas ; Khennouf, Lila ; Madry, Christian ; Gong, Hui ; Richard-Loendt, Angela ; Huang, Wenhui ; Saito, Takashi ; Saido, Takaomi C. ; Brandner, Sebastian ; Sethi, Huma ; Attwell, David. / Amyloid β oligomers constrict human capillaries in alzheimer’s disease via signaling to pericytes. In: Science. 2019.
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AU - Jaunmuktane, Zane

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AU - Saito, Takashi

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