Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-β and Prevents Alzheimer's Disease-Type Pathology and Cognitive Deficits

Deficiencies in the clearance of peripheral amyloid beta (A beta) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose A beta is decreased in AD. However, the exact mechanism of A beta clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of A beta. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose A beta in vivo and in vitro. Moreover, enhancing blood monocyte A beta phagocytosis by improving energy metabolism alleviated brain A beta deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired A beta phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.

Automated summary

A study found that decreased energy metabolism in blood monocytes is associated with cellular senescence, dysfunctional phagocytosis of amyloid beta (A beta), and the progression of Alzheimer's disease (AD). Improving energy metabolism rejuvenates monocytes and enhances their ability to phagocytose A beta, leading to reduced A beta deposition and neuroinflammation, and improved cognitive function in AD mice. This study reveals a new mechanism of impaired A beta phagocytosis in monocytes and suggests restoring energy metabolism as a novel therapeutic strategy for AD.