Internal medicine

Pathology

Cerebral blood flow

Neuroscience

Disease

Pathogenesis

Central nervous system

Biology

Blood flow

Immunology

Blood–brain barrier

Alzheimer's disease

Medicine

Nature Neuroscience

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. The authors found that white blood cells plug about 2% of capillaries in the brains of Alzheimer’s disease mouse models. When the adhesion of these cells was blocked, cerebral blood flow immediately increased and cognitive performance rapidly improved.

Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models