An update on potential links between type 2 diabetes mellitus and Alzheimer’s disease

• Published in: Molecular biology reports 2020-08, Vol.47 (8), p.6347-6356
• Main Authors: De Sousa, Ricardo Augusto Leoni, Harmer, Alison R., Freitas, Daniel Almeida, Mendonça, Vanessa Amaral, Lacerda, Ana Cristina Rodrigues, Leite, Hércules Ribeiro
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - etiology; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Animal Anatomy; Animal Biochemistry; Animals; Biomedical and Life Sciences; brain; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Dyslipidemia; glucose; Glucose - metabolism; Histology; Humans; Hyperglycemia; hyperlipidemia; Inflammation; Inflammation - etiology; Inflammation - metabolism; Inflammation - pathology; Insulin; Insulin - metabolism; Insulin receptor substrate 1; Insulin Receptor Substrate Proteins - metabolism; Insulin receptors; Insulin Resistance; Life Sciences; Literature reviews; Metabolism; Morphology; Neurodegenerative diseases; Neurogenesis; neurons; noninsulin-dependent diabetes mellitus; obesity; Plaques; Review
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-020-05693-z

Alzheimer’s disease (AD) and type 2 diabetes (T2D) major feature is insulin resistance. Brain and peripheral insulin resistance lead to hyperglycemia, which contributes to the development of T2D-linked comorbidities, such as obesity and dyslipidemia. Individuals with hyperglycemia in AD present with neuronal loss, formation of plaques and tangles and reduced neurogenesis. Inflammation seems to play an essential role in the development of insulin resistance in AD and T2D. We conducted a literature review about the links between AD and T2D. Alterations in glucose metabolism result from changes in the expression of the insulin receptor substrates 1 and 2 (IRS-1 and IRS-2), and seem to be mediated by several inflammatory pathways being present in both pathologies. Although there are some similarities in the insulin resistance of AD and T2D, brain and peripheral insulin resistance also have their discrete features. Failure to activate IRS-1 is the hallmark of AD, while inhibition of IRS-2 is the main feature in T2D. Inflammation mediates the alterations in glucose metabolism in AD and T2D. Targeting inflammation and insulin receptors may be a successful strategy to prevent and ameliorate T2D and AD symptoms.