Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer's disease mouse models. Academic Article uri icon

Overview

abstract

  • Cerebral blood flow (CBF) reductions in Alzheimer's disease patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences for Alzheimer's disease pathogenesis remain poorly understood. In APP/PS1 and 5xFAD mice we found that an increased number of cortical capillaries had stalled blood flow as compared to in wild-type animals, largely due to neutrophils that had adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to both an immediate increase in CBF and rapidly improved performance in spatial and working memory tasks. This study identified a previously uncharacterized cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of Alzheimer's disease and demonstrated that improving CBF rapidly enhanced short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a strategy for improving cognition in Alzheimer's disease patients.

publication date

  • February 11, 2019

Research

keywords

  • Alzheimer Disease
  • Brain
  • Memory
  • Neutrophils

Identity

PubMed Central ID

  • PMC6508667

Scopus Document Identifier

  • 85061348146

Digital Object Identifier (DOI)

  • 10.1109/TSMC.1979.4310076

PubMed ID

  • 30742116

Additional Document Info

volume

  • 22

issue

  • 3