Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the accumulation of misfolded proteins in the brain. Recently, the impact of blood components in the progression of this disease has come to attention. This study investigates the effects of infusing blood from young and old wild-type mice into transgenic mice that model AD brain amyloidosis. Impaired memory and A? accumulation were observed in mice infused with blood from old donors. A proteomic analysis in the brain of these mice identified alterations in components related to synaptogenesis and the endocannabinoid system. The ?2?2 protein, associated with neuronal calcium regulation, was validated as a possible mediator of the observed effects. This study highlights the influence of blood in AD pathology and the identification of potential therapeutic targets. © 2025 Pizarro et al.