A novel therapeutic prospect: a dual-acting tirzepatide for Alzheimer's disease.

Alzheimer's disease (AD), the leading cause of dementia, involves microglial activation, pro-inflammatory cytokine release, and impaired insulin signaling via insulin receptor substrate 1 (IRS-1) inhibition. Brain insulin resistance (BIR) is a key factor in AD progression, disrupting synaptic plasticity and neuronal function. Additionally, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) signaling, which regulate insulin pathways, are compromised in AD. GLP-1/GIP receptor activation or their analogs, such as tirzepatide, show potential in mitigating AD neuropathology. However, the precise neuroprotective mechanisms of tirzepatide remain unclear. This mini-review explores tirzepatide's potential therapeutic effects in AD, focusing on its role in restoring insulin signaling, reducing neuroinflammation, and improving cognitive function. Understanding these mechanisms could offer new insights into AD treatment strategies.