Crucial players in Alzheimer’s disease and diabetes mellitus: Friends or foes?

• Published in: Mechanisms of ageing and development Vol. 181; pp. 7 - 21
• Main Authors: Kubis-Kubiak, AM, Rorbach-Dolata, A., Piwowar, A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-07-2019
• Subjects: Alzheimer’s disease; Amyloid β; Diabetes mellitus; Hyperglycaemia; Insulin resistance; Tau protein; Insulin resistance; Hyperglycaemia; Alzheimer’s disease; Tau protein; Diabetes mellitus; Amyloid β
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2019.03.008

•The association of the disturbances in glucose and insulin brain homeostasis with AD development is under investigation.•The comorbidity between T2DM and AD is so strong that new distinct clinical state was characterized and named T3DM.•Aβ formation is strongly depended on insulin, hyperglycaemia and advanced glycation end product metabolisms.•The impact of diabetic factors on tau protein phosphorylation or dephosphorylation processes is still not fully understood.•Valuation of possible biomarkers of T3DM would be a prominent step for diagnosis and risk assessment of this disease.
Alzheimer's disease (AD) and diabetes mellitus, especially type 2 (T2DM), are very common and widespread diseases in contemporary societies, and their incidence is steadily on the increase. T2DM is a multiple metabolic disorder, with several mechanisms including hyperglycaemia, insulin resistance, insulin receptor and insulin growth factor disturbances, glucose toxicity, formation of advanced glycation end products (AGEs) and the activity of their receptors. AD is the most common form of dementia, characterized by the accumulation of extracellular beta amyloid peptide aggregates and intracellular hyper-phosphorylated tau proteins, which are thought to drive and/or accelerate inflammatory and oxidative stress processes leading to neurodegeneration.
The aim of this paper is to provide a comprehensive review of the evidence linking T2DM to the onset and development of AD and highlight the unknown or poorly studied “nooks and crannies” of this interesting relationship, hence providing an opportunity to stimulate new ideas for the analysis of comorbidities between AD and DM. Despite, indication of possible biomarkers of early diagnosis of T2DM and AD, this review is also an attempt to answer the question as to whether the crucial factors in the development of both conditions support the link between DM and AD.