Amyloid b 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 journalArticlepeer-review

76 Scopus citations

Abstract

Cerebral blood flow is reduced early in the onset of 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. 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 b (Ab) constricts brain capillaries at pericyte locations. This was caused by Ab 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 Ab could potentially reduce energy lack and neurodegeneration in AD.

Original languageEnglish (US)
Article numbereaav9518
JournalScience
Volume365
Issue number6450
DOIs
StatePublished - Jul 19 2019

ASJC Scopus subject areas

  • General

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