Aging is known to be one of the top risk factors for both Alzheimer's disease (AD) and Type 2 Diabetes (T2D). The pathologies of these disorders are somewhat understood, with AD being associated with the accumulations of amyloid-β plaques and/or phosphorylated tau tangles (two proteins involved in neuron structure and development) and T2D being associated with resistance to insulin (the growth factor that controls glucose uptake by cells). For many years these two diseases have been treated separately, with few overlaps. In more recent years, however, the overlap between them has become more prominently recognized. The rate of AD in diabetic individuals is elevated, and it may be worth considering these two "separate" disorders as a related problem.
Could Alzheimer's disease, a deadly form of dementia, also be considered a type of diabetes? (Image Source: National Institute of Aging)
The first suggestion of AD being a previously unrecognized type of diabetes was in 2005, where it was noted that insulin signaling and insulin-like growth factor (IGF) expression were greatly affected in the instance of AD. It has since been shown that in the instance of AD, IGF, insulin receptor, and insulin expression are all reduced in the temporal cortex and hippocampus of the brain. Further, as AD progresses the levels of these gene transcripts continue to decrease. These inhibited insulin-related signals result in a deficiency and similar symptoms to those shown in other cases of diabetes. This deficiency also contributes to a vicious cycle, as impaired insulin receptor expression can contribute to further AD-like pathology such as hyperphosphorylation of tau and increased amyloid-β deposits as well as decreased clearance of these deposits from the brain.
Additional issues that arise from inhibited insulin signaling in the brain include dysregulation of glucose transporter proteins, which results in improper glucose transport and usage, as well as increased oxidative stress and mitochondrial dysfunction within the neurons. It is uncertain whether or not the changes in insulin signaling are causal of AD, but this alternative perspective could provide new approaches to understanding the methods by which AD develops. AD brains display similar biochemical properties to those affected by T2D, so it may be worthwhile to consider these similarities as being due to a singular cause. The two diseases even show a similar response to diet, with both being exacerbated by a high-fat diet in animal models (although it's worth noting that dietary modulation is widely considered as a preventative measure for most age-related disorders).
Although seldom considered a metabolic disorder, it is clear that AD is metabolically affected in a similar fashion to diabetes. Although frequently treated separately, the same basic principles which are used for diagnosing an individual as diabetic may also be applied to understand some of the mechanisms affected in AD. As such, it may be appropriate to consider AD as a type of diabetes of the brain. Recent in vivo and clinical trials have investigated potential treatments for the overlapping symptoms of T2D and AD. Although results using diabetes drugs such as Metformin are conflicted, ongoing preliminary experiments using Exendin-4 have provided promising enough results to warrant further investigation in human subjects.
Since the rate of diabetes is ever-increasing worldwide, understanding how it is related to AD may be key in understanding the impact of both diseases. This could provide further insights into preventative and curative measures for both of these deadly disorders at the same time. - Kenny Wilson
