Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Krug, R.
The connection between Alzheimer's disease and type 2 diabetes mellitus: a review of recent findings and the potential of antidiabetic drugs in the treatment of Alzheimer's disease
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2018. pp. 61
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Holzer Ulrike
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- Abstract:
- This literature review investigates the pathophysiological similarities between T2DM and AD and aims to provide an overview of current research and the outcomes of antidiabetic treatment used in the setting of AD. Mitochondrial dysfunction, oxidative stress, impaired insulin metabolism, hyperglycaemia, GSK-3ß activation, chronic inflammation, changes in the brain’s neuronal structure together with cognitive decline and amyloidogenesis seem to link these both conditions. Some of the links have been associated with increased levels of Aß and tau tangle formation and therefore thought to promote AD pathology. Some publications refer to AD even as a diabetic condition of the brain. Especially the facts that glucose uptake in the brain is only partly independent of insulin and that AD and T2DM have both been associated with brain insulin resistance, throw a new light on the role of insulin and raise a number of further questions. The whole impact of brain IR in AD is not clear yet, but it has also been suggested to play a part in other neurodegenerative conditions. However, it was not possible to associate systemic IR with increased Aß load in CSF and PET imaging. Although, on a structural level, neuroimaging showed that the changes in the brains of T2DM and AD patients are indeed similar in a significant way. In terms of the antidiabetic medications that could be suitable for AD, intranasal insulin application, TZDs, GLP-1 agonists, DPP4 inhibitors, metformin and amylin have drawn the most attention regarding preclinical and clinical outcomes, and almost all of them cross the BBB. In preclinical studies, virtually all the antidiabetic agents were associated with lowering the biomarkers for AD, reducing inflammatory response and improving cognitive performance in specific mouse models. In humans in particular intranasal insulin application stood out because it improved verbal memory in AD patients with a negative APOE-4 genotype and its administration proved to be safe also for nondiabetic people.