Full text is available at the source.
Abstract
Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are increasingly prevalent, particularly with age.
- AD may be conceptualized as 'type 3 diabetes,' indicating a metabolic disease linked to insulin resistance in the brain.
- Shared molecular mechanisms between T2DM and AD include chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, and impaired glucose metabolism.
- Insulin resistance could increase glycogen synthase kinase 3β (GSK-3β) activity, leading to tau hyperphosphorylation and amyloid-β accumulation.
- The NOD-like receptor protein 3 (NLRP3) inflammasome and O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) are critical mediators that connect metabolic dysfunction to neurodegeneration.
- Emerging therapeutic targets may include the NLRP3 inflammasome and O-GlcNAcylation, which could bridge T2DM and AD.
- Various antidiabetic agents, like glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, may offer new treatment options for AD.
Simplified