Mechanisms of Association between Alzheimer's disease and Diabetes Mellitus: The Insulin Paradox

Abstract

Between Alzheimer's Disease (AD) and Diabetes Mellitus (DM) it has been evidenced that there are multiple mechanisms in common in both pathologies, ranging from cognitive deterioration in the clinical aspect to biochemical alterations of which the following can be highlighted; the increase in pro-inflammatory agents and excitotoxicity, increase in oxidative stress and increase in the final products of advanced glycation (AGEs), alterations in glucose metabolism, as well as alterations in the mTORC1 /S6 and GSK-3 pathways β; It also highlights the role of Insulin Resistance (Ri), where this alteration is linked to both AD and MD at various points in their physiopathology, either by influencing the different mechanisms mentioned above or directly. Objective. It is described how the influence of this hormone is such, whether its levels are high, effect known as hyperinsulinism or low effect known as hypoinsulinism, since both extremes lead to neurodegenerative effects characteristic of AD, mainly in the increase of β amyloid (Aβ) and hyperphosphorylated tau (pTau), through different processes. Contribution. It is based on this phenomenon that we describe what we call "The insulin paradox", in which the insulin/PI3K/Akt pathway also stands out as a crucial point, since independently of hyper or hypoinsulinism conditions this pathway is altered in both scenarios. This relationship between AD and DM is considered from the point of view of hypoglycemic treatments aimed at the attention of DM, which seem to interfere with AD, through several of the mechanisms in common that these pathologies have. Conclusion. Although it is too early to consider that these treatments for DM will give the same results in cases of AD, these data are valuable precedents in the search for therapeutic alternatives for AD.