Diabetes and Tau Hyperphosphorylation
Some researchers consider the metabolic dysfunction of brain tissue in Alzheimer's disease to be similar to that produced by diabetes, both involving disruption of insulin signaling. It was proposed at one point that Alzheimer's should be classified as type 3 diabetes. Diabetic patients have an increased risk of Alzheimer's disease, but it is possible to argue that this is the outcome of raised inflammation. Here, researchers dig a little deeper to instead suggest that a specific regulatory aspect of the diabetic metabolism leads to an increase in the tau pathology characteristic of Alzheimer's disease, and that this mechanism links the two conditions.
Diabetes mellitus is characterized by hyperglycemia caused by a lack of insulin, insulin resistance, or both. It is associated with the development of secondary complications resulting in several comorbidities. Recent studies have revealed an increased risk of developing cognitive dysfunction or dementia in diabetes patients. Diabetes mellitus is considered a risk factor for many neurodegenerative diseases, including Alzheimer's disease (AD). There is increasing evidence to support a link between diabetes mellitus and AD. Studies have shown the dysfunction of insulin signaling in the brain, resulting in increased tau protein phosphorylation (hyperphosphorylation), a hallmark and biomarker of AD pathology, leading to accumulation of neurofibrillary tangles.
In diabetes mellitus, the insulin dysfunction in the brain is reported to alter the glycogen synthase kinase-3β (GSK-3β) activity showing to enhance tau phosphorylation. In diabetes mellitus and AD, GSK-3β signaling has been involved in the physiological and pathological processes, respectively. This potentially explains why diabetes mellitus patients have an increased risk of developing AD with disease progression and aging.
Interestingly, several in vivo studies with oral antidiabetic drugs and insulin treatment in diabetes mellitus have improved cognitive function and decreased tau hyperphosphorylation. This article will review the relationship between diabetes mellitus and AD as it relates to tau pathology. More understanding of the link between diabetes mellitus and AD could change the approach researchers and clinicians take toward both diseases, potentially leading to new treatments and preventative strategies in the future.