Platelet factors attenuate inflammation and rescue cognition in ageing

Identifying therapeutics to delay, and potentially reverse, age-related cognitive decline is critical in light of the increased incidence of dementia-related disorders forecasted in the growing older population(1). Here we show that platelet factors transfer the benefits of young blood to the ageing brain. Systemic exposure of aged male mice to a fraction of blood plasma from young mice containing platelets decreased neuroinflammation in the hippocampus at the transcriptional and cellular level and ameliorated hippocampal-dependent cognitive impairments. Circulating levels of the platelet-derived chemokine platelet factor 4 (PF4) (also known as CXCL4) were elevated in blood plasma preparations of young mice and humans relative to older individuals. Systemic administration of exogenous PF4 attenuated age-related hippocampal neuroinflammation, elicited synaptic-plasticity-related molecular changes and improved cognition in aged mice. We implicate decreased levels of circulating pro-ageing immune factors and restoration of the ageing peripheral immune system in the beneficial effects of systemic PF4 on the aged brain. Mechanistically, we identified CXCR3 as a chemokine receptor that, in part, mediates the cellular, molecular and cognitive benefits of systemic PF4 on the aged brain. Together, our data identify platelet-derived factors as potential therapeutic targets to abate inflammation and rescue cognition in old age.

Automated summary

It is crucial to find therapeutics that can delay or reverse age-related cognitive decline, considering the increasing incidence of dementia-related disorders in the aging population. This study demonstrates that platelet factors can transfer the beneficial effects of young blood to the aging brain. When aged mice were systemically exposed to a fraction of young mouse plasma containing platelets, neuroinflammation in the hippocampus decreased, leading to improvements in hippocampal-dependent cognitive impairments. The study also identified platelet-derived chemokine PF4 as a potential therapeutic target to reduce inflammation and improve cognition in old age.