Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, neurofibrillary tangles, and cognitive decline. Given the shared neuropathophysiological traits between AD and type 2 diabetes mellitus (T2DM), repurposing antidiabetic medications, such as dipeptidyl peptidase 4 inhibitors (DPP4i), has emerged as a promising therapeutic strategy. This review comprehensively evaluates the preclinical and clinical evidence supporting the potential of DPP4i in preventing or treating AD by modulating Aβ and tau pathology, improving cognitive function, reducing neuroinflammation and oxidative stress, and promoting neuronal survival. The beneficial effects of DPP4i are likely mediated through the modulation of insulin signaling, anti-inflammatory and antioxidant properties, glucagon-like peptide-1 (GLP-1) upregulation, and modulation of the amyloidogenic pathway. While further research is needed to establish their clinical efficacy in AD patients, DPP4i offers a promising avenue for therapeutic intervention for this devastating neurodegenerative disease.

MeSH

Diabetes Mellitus, Glucagon-Like Peptide 1, Plaque, Amyloid, Alzheimer Disease, Dipeptidyl-Peptidase Iv Inhibitors, Therapeutics, Amyloid, Neurodegenerative Diseases, Diabetes Mellitus, Type 2

Cited by

• Comparative efficacy and safety of antidiabetic agents in Alzheimer's disease: A network meta-analysis of randomized controlled trials. J Prev Alzheimers Dis, 2025