The recent study from the Daegu Gyeongbuk Institute of Science and Technology reveals that overexpression of somatostatin (SST) in a mouse model of Alzheimer’s disease significantly reduces inflammation and amyloid β burden, leading to improved cognitive function. SST, a neuropeptide primarily produced in neurons, exerts its effects mainly on microglia, the brain’s resident immune cells. This research demonstrates that SST can mitigate microglial hyperactivation, a key feature associated with Alzheimer’s pathology, by binding to somatostatin receptors (SSTR2) expressed on microglia.

The findings highlight the therapeutic potential of targeting the SST signaling pathway, particularly given that SST levels are diminished in Alzheimer’s patients. In vitro experiments showed that SST treatment enhanced the phagocytic activity of microglia, promoting the clearance of amyloid β. The in vivo results were compelling; SST overexpression in the dentate gyrus of 5xFAD mice led to reduced microglial activation and improved spatial memory, even in late-stage disease models. Importantly, the study suggests that SST can shift microglial states toward a less inflammatory profile, potentially offering a neuroprotective effect.

This research underscores a pivotal shift in Alzheimer’s therapeutic strategies, moving away from solely targeting amyloid β and tau proteins to include modulation of neuroinflammation via SST. The existence of approved drugs that target SST receptors opens avenues for repurposing these agents for Alzheimer’s treatment, potentially accelerating the development of effective therapies. As Professor Jiwon Um notes, this study lays the groundwork for leveraging existing medications to address the complex neuroinflammatory components of dementia, presenting a promising frontier in the fight against Alzheimer’s disease.

Source: lifespan.io