It’s highly accepted in the medical field that type 2 diabetes is a risk factor for Alzheimer’s Disease (AD). This is likely due to the reduced blood flow to the brain as a result of damaged blood vessels. This results in a reduced supply of essential nutrients to the brain and eventual impairment.
The Third Type
But less accepted is the new theory of type 3 diabetes. This is a term which describes the hypothesis that Alzheimer’s disease may be triggered by insulin resistance and insulin-like growth factor dysfunction that occurs in the brain. Type 3 diabetes occurs when brain cells become unresponsive to insulin (due to disruption in receptors and signaling), which regulates the amount of glucose in the blood, a process which is essential for brain functions such as memory and learning.
A growing body of research indicates that insulin resistance in the central nervous system plays a key role in cognitive decline involved in dementias such as Alzheimer’s disease. Research indicates that many of the molecular, biochemical, and tissue lesions present in Alzheimers could be accounted for by disturbances in vital brain insulin and insulin-like growth factor (IGF) signaling processes.
Animal studies show that inducing diabetes in the brains of mice results in Alzheimer’s-like alterations in brain tissue, while administration of diabetes medication to mice alleviates some of the symptoms of cognitive impairment in mice experiencing induced insulin resistance in the brain. In other words, diabetes in the brain seems to produce similar pathology as Alzheimer’s disease, and treating diabetes in the brain of mice with diabetes medication seems to relieve reductions in brain function.
However, further research demonstrates that this Alzhimers-like pathology and reductions in cognitive functioning sometimes occur in the absence of type 1 and type 2 diabetes. Data reflect that while obesity and type 2 diabetes may be risk factors for brain insulin resistance and even for Alzheimer’s-like neurodegeneration in brain tissue, it does not account for this pathology on its own. In other words, type 1 or 2 diabetes alone is not sufficient to cause Alzheimer’s. This suggests that a third type of diabetes, specific to the central nervous system may be at play. This would account for Alzheimer-s like neurodegeneration in the absence of the first two types of diabetes. Genetic research surrounding Alzheimer’s disease seems to confirm this theory.
Genetic Links
The APOE4 gene, which is present in about 20 percent of the population and over half of those affected by Alzheimer’s disease, has also been linked to interference with neuronal capacities to use insulin. The APOE 4 protein which is produced by the gene binds to insulin receptors on the surfaces of neurons, blocking the receptor and eventually invading the cell which disrupts insulin signal processing. This genetic resistance eventually causes brain cells to starve and die. This results in cognitive impairments often specific to memory and learning.
Animal studies showed that the APOE4 gene combined with a high-fat diet in mice resulted not only in insulin impairment (especially in elderly mice) but also in eventual insulin resistance in the brain. Alternately, in examining treatments for insulin resistance in the brain, clinical trials of intranasal insulin sprays show some progress in slowing cognitive decline. This suggests that administration of diabetes-like medication to the brain may address diabetic-induced cognitive decline and perhaps even Alzheimers. All of this mounting evidence is why Alzheimer’s disease is increasingly becoming known as type 3 diabetes.
While further research must be conducted to firmly solidify this theory, the idea that Alzheimers may represent a form of type 3 diabetes which involves selective insulin resistance is most probable. The theory is supported by molecular and biochemical features which mimic the overlapping features of the two conditions. Additionally, genetic animal and human research continues to indicate this theory may be correct. Therefore, current data strongly suggest Alzheimers may be a neuroendocrine disease, not solely a cognitive one.
References:
deWidt, L. (2017). Researchers link Alzheimer’s gene to Type 3 diabetes. The Mayo Clinic.
Dennis, D. (2017). Mayo Clinic Minute: Is Alzheimer’s Type 3 diabetes?. The Mayo Clinic.
de la Monte, S. M., & Wands, J. R. (2008). Alzheimer’s disease is type 3 diabetes-evidence reviewed. Journal of diabetes science and technology, 2(6), 1101–1113. https://doi.org/10.1177/193229680800200619
