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Review
. 2020 May;10(5):e01577.
doi: 10.1002/brb3.1577. Epub 2020 Mar 14.

Neurodegeneration in type 2 diabetes: Alzheimer's as a case study

Jalaja Madhusudhanan  1 , Gowthaman Suresh  1 , Vasudharani Devanathan  1
Affiliations
Review

Neurodegeneration in type 2 diabetes: Alzheimer's as a case study

Jalaja Madhusudhanan et al. Brain Behav. 2020 May.

Abstract

Introduction: Rigorous research in the last few years has shown that in addition to the classical mechanism of neurodegeneration, certain unconventional mechanisms may also lead to neurodegenerative disease. One of them is a widely studied metabolic disorder: type 2 diabetes mellitus (T2DM). We now have a clear understanding of glucose-mediated neurodegeneration, mostly from studies in Alzheimer's disease (AD) models. AD is recognized to be significantly associated with hyperglycemia, even earning the term "type 3 diabetes." Here, we review first the pathophysiology of AD, both from the perspective of classical protein accumulation, as well as the newer T2DM-dependent mechanisms supported by findings from patients with T2DM. Secondly, we review the different pathways through which neurodegeneration is aggravated in hyperglycemic conditions taking AD as a case study. Finally, some of the current advances in AD management as a result of recent research developments in metabolic disorders-driven neurodegeneration are also discussed.

Methods: Relevant literatures found from PubMed search were reviewed.

Results: Apart from the known causes of AD, type 2 diabetes opens a new window to the AD pathology in several ways. It is a bidirectional interaction, of which, the molecular and signaling mechanisms are recently studied. This is our attempt to connect all of them to draw a complete mechanistic explanation for the neurodegeneration in T2DM. Refer to Figure 3.

Conclusion: The perspective of AD as a classical neurodegenerative disease is changing, and it is now being looked at from a zoomed-out perspective. The correlation between T2DM and AD is something observed and studied extensively. It is promising to know that there are certain advances in AD management following these studies.

Keywords: Alzheimer's disease; neurodegeneration; type 2 diabetes mellitus; type 3 diabetes.

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Conflict of interest statement

Authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Graphical representation of the estimated number of AD and Diabetes patients worldwide. It shows a steady increase in the number of AD patients along with the huge increase in diabetic patients every year, indicating a strong correlation between them. The numbers for 2030 and 2040 are extrapolated from the current statistics. (Sources: IDF (International Diabetes Federation), ADI (Alzheimer's Disease International) and WHO (World Health Organization). Data points are the estimates reported in the websites of these organizations, and they are compiled and represented as a histogram for comparison)
Figure 2
Figure 2
Comparison between the role of amylin (IAPP) in T2DM patients and Aβ (beta‐amyloid) in AD patients. It supports the fact that the dysfunction and accumulation of Amyloidogenic peptides are common causes for both the pathologies. Amylin is now considered as one of the prominent links in the molecular mechanism of glucose‐mediated neurodegeneration
Figure 3
Figure 3
Schematic representation of the different mechanisms involved in glucose‐mediated neurodegeneration. Impaired insulin signaling is at the center in T2DM patients, which leads to various AD symptoms and then ultimately to the neuronal cell death
See this image and copyright information in PMC

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