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Type 3 Diabetes? How Alzheimer’s Disease Might Be Related to Insulin Resistance
An emerging hypothesis in Alzheimer’s disease researchmay come as a surprise. Accumulating evidence supports a close relationship between Alzheimer’s disease and diabetes. While the two disorders are typically studied in complete isolation from one another, several laboratories have begun to unearth a metabolic component to the pathology of Alzheimer’s disease (AD).
The hallmark and diagnostic feature of AD is the presence of amyloid-β plaques in the brains of patients. Most research has focused on these plaques as causative agents of neurodegeneration. But, what if the plaques were instead a consequence of a neurodegenerative process? What if research into Alzheimer’s therapy focused more on changes in the brain that come before the production of amyloid-β plaques? This is where insulin research comes in.
Previous research has shown that diabetes patients have an increased risk of neurodegenerative diseases like AD (de la Monte et al., 2009). Furthermore, insulin resistance has been demonstrated in patients with AD, and inhibition of proper insulin signaling can contribute to AD-type neurodegeneration (Hoyer, 2004). Also, deficits in insulin signaling and decline in brain glucose utilization are seen alongside increased severity of AD symptoms (Frolich et al., 1998).
Dr. Suzanne De La Monte, who champions the metabolic hypothesis of Alzheimer’s disease, has gone so far as to dub AD “Type 3 diabetes.” She hypothesizes that “brain diabetes” results when insulin resistance and insulin deficiency lead to the production of amyloid-β plaques. She goes on to specify that diabetes medication has had unclear effects on Alzheimer’s patients in clinical trials. However, this may be because the disease process is too far along by the time patients seek treatment. De La Monte’s research focuses on the preventative potential of a healthy diet and she champions prevention as an important research focus for the future.
This work is an encouraging example of approaching scientific dilemmas from another angle. We hope this leads to great advancements, and can’t wait to hear what happens next!
What do you think?
Could other disorders be related that are usually studied in complete isolation?
Could insulin resistance lead to other neurodegenerative disorders?
Ahmad. (2012). Overlapped metabolic and therapeutic links between Alzheimer and diabetes. Mol Neurobiol. [Epub ahead of print]
de la Monte, SM. (2012). Brain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimer’s Disease. Current Alzheimer Research. 9, 35-66 .
de la Monte SM, Tong M, Lawton M, Longato L. (2009). Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment. Mol Neurodegener. Dec 24;4:54.
Frolich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S. (1998). Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease. J Neural Transm 105(4-5):423-438.
Hoyer S. (2004). Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol 490(1-3):115-125.