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

• DOI: 10.1126/science.aav9518
• Publication Date: 2019-06-20T23:15:12Z
• Authors: Ross Nortley; Nils Korte; Pablo Izquierdo; Chanawee Hirunpat...; Anusha Mishra; Zane Jaunmuktane; Vasiliki Kyrargyri; Thomas Pfeiffer; Lila Khennouf; Christian Madry; Hui Gong; Angela Richard-Lo...; Wenhui Huang; Takashi Saito; Takaomi C. Saido; Sebastian Brandner; Huma Sethi; David Attwell
• Keywords: Pericyte; Arteriole; Cognitive Decline; Constriction; Human brain

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