Pathophysiological link between Alzheimer’s disease and type 2 diabetes mellitus: novel therapeutic applications of anti-diabetic drugs

Abstract

This review aims to distinguish type 2 diabetes (T2D) and Alzheimer’s disease (AD) as independent illnesses, while also highlighting the relationship of insulin resistance (IR) between the two conditions. Elucidating a similar mechanism of IR in T2D and AD may uncover the potential for diabetic therapies to treat AD. The cause of AD is unknown, although it is established that T2D is a major risk factor. The focus of this review will be to: 1. examine the mechanistic cross-talk between insulin-mediated signalling pathways in both T2D and AD; 2. highlight the similar cellular structural changes in the brain associated with cognitive impairments in both T2D and AD; and, 3. assess the effectiveness of diabetic therapies to ameliorate AD-related cognitive impairments. AD has been described as a brain-specific diabetes due to the presence of IR within regions of the brain exhibiting high insulin signalling and insulin receptor expression (e.g., the hippocampus). IR is associated with decreased hippocampal glucose metabolism in AD and T2D, leading to cognitive impairments. Future longitudinal studies should be conducted on AD-predisposed populations, or individuals exhibiting early signs of AD, to assess the effectiveness of diabetic therapies on outcomes associated with cognitive impairments before irreversible complications arise.</p