“Diabetes is a disease which often shows itself in families in which insanity prevails.” Sir HenryMaudsley, The Pathology ofMind, 1879.
There are several oxidative stress-related pathways interconnecting Alzheimer’s disease and type II diabetes, two public health problems worldwide. Coincidences are so compelling that it is attractive to speculate they are the same disorder. However, some pathological mechanisms as observed in diabetes are not necessarily the same mechanisms related to Alzheimer’s or the only ones related to Alzheimer’s pathology. Oxidative stress is inherent to Alzheimer’s and feeds a vicious cycle with other key pathological features, such as inflammation and ionic calcium (Ca2+) dysregulation. Alzheimer’s pathology by itself may lead to insulin resistance in brain, insulin resistance being an intervening variable in the neurodegenerative disorder. Hyperglycemia and insulin resistance from diabetes, overlapping with the Alzheimer’s pathology, aggravate the progression of the neurodegenerative processes, indeed. But the same pathophysiological background is behind the consequences, oxidative stress. We emphasize oxidative stress and its detrimental role in some key regulatory enzymes.
Biochim Biophys Acta. 2016 Aug 25. pii: S0925-4439(16)30215-0. doi: 10.1016/j.bbadis.2016.08.018. [Epub ahead of print]
Is Alzheimer’s disease a Type 3 Diabetes? A critical appraisal.
Kandimalla R1, Thirumala V2, Reddy PH3.
Recently researchers proposed the term ‘Type-3-Diabetes’ for Alzheimer’s disease (ad) because of the shared molecular and cellular features among Type-1-Diabetes, Type-2-Diabetes and insulin resistance associated with memory deficits and cognitive decline in elderly individuals. Recent clinical and basic studies on patients with diabetes and AD revealed previously unreported cellular and pathological among diabetes, insulin resistance and AD. These studies are also strengthened by various basic biological studies that decipher the effects of insulin in the pathology of AD through cellular and molecular mechanisms. For instance, insulin is involved in the activation of glycogen synthase kinase 3β, which in turn causes phosphorylation of tau, which involved in the formation of neurofibrillary tangles. Interestingly, insulin also plays a crucial role in the formation amyloid plaques. In this review, we discussed significant shared mechanisms between AD and diabetes and we also provided therapeutic avenues for diabetes and AD. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases – edited by P. Hemachandra Reddy.
Copyright © 2016 Elsevier B.V. All rights reserved.
Alzheimer’s disease; BMI; GSK3β; MCI amyloid beta; Obesity; Tau; Type-3-Diabetes; diabetes
PMID: 27567931 DOI: 10.1016/j.bbadis.2016.08.018