Incretin Mimetics as Potential Disease Modifying Treatment for Alzheimer’s Disease

Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?

Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry

Article type: Review Article

Authors: Crook, Harry^a | Edison, Paul^{a; b; *}

Affiliations: [a] Faculty of Medicine, Imperial College London, London, UK | [b] Cardiff University, Cardiff, UK

Correspondence: [*] Correspondence to: Prof. Paul Edison, MD, PhD, MPhil, FRCP, FRCPI, Professor of Neuroscience, Imperial College London, Commonwealth Building, Hammersmith Campus, Imperial College London, London, UK. E-mail: [email protected].

Abstract: Alzheimer’s disease is a devastating neurodegenerative condition that exerts a significant global burden. Despite recent efforts, disease modifying therapies remain extremely limited, with a tremendous proportion of patients having to rely on symptomatic treatment only. Epidemiological and pathological overlaps exist between Alzheimer’s disease and diabetes mellitus type 2, with people with diabetes mellitus type 2 at a significantly increased risk of developing Alzheimer’s disease in the future. Incretin mimetics, also known as GLP-1/GIP receptor agonists, are useful tools licensed for the treatment of diabetes mellitus type 2 which have recently been the subject of news coverage for their off-label use as weight loss medications. Emerging evidence highlights the possible neuroprotective function of incretin mimetics in models of Alzheimer’s disease as well as in clinical studies. This review details the pre-clinical and clinical studies that have explored the effectiveness of incretin mimetics to alleviate Alzheimer’s disease associated pathology and cognitive impairment, while also highlighting the progress made to examine the effectiveness of these molecules in Parkinson’s disease. Should clinical trials prove effective, incretin mimetics may be able to be repurposed and become useful novel tools as disease-modifying treatments for Alzheimer’s disease and other neurodegenerative diseases.

Keywords: Alzheimer’s disease, drug repositioning, gastric inhibitory polypeptide, glucagon-like peptide-1, type 2 diabetes mellitus

DOI: 10.3233/JAD-240730

Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S357-S370, 2024