Project Summary: A Spicy Situation in Alzheimer's Disease

Alzheimer’s disease, the fifth leading cause of death in people ages 65 and older, is a neurodegenerative disorder characterized by neurofibrillary tangles and a buildup of β-amyloid plaques in the brain. Environmental and genetic risk factors contribute to the development of Alzheimer’s disease, such as  type 2 diabetes. Type 2 diabetes has shown significant connections to Alzheimer’s disease in insulin resistance and inflammation. In people with type 2 diabetes, neuronal insulin resistance leads to the accumulation of β-amyloid and disrupted synaptic function which lead to Alzheimer's. 

In Alzheimer's disease, the brain is insulin deficient and thus the neurons cannot take in glucose for energy to perform their functions. Intranasal administration of insulin has been shown to be beneficial to cognition in Alzheimer's patients. I proposed the use of insulin sensitizers which are used for type 2 diabetes patients. However, in vitro studies have shown that metformin, an insulin sensitizing drug, increases the amount of β-amyloid. I found that cinnamon contains anti-oxidizing and insulin sensitizing polyphenols. Thus, I tested both metformin and cinnamon on cells that produce β-amyloid protein to see their effects on the amount of β-amyloid.

I found that metformin causes cells to produce double the amount of β-amyloid as untreated cells and that cinnamon causes a 125% increase in β-amyloid. Given these results, insulin sensitizers may be exacerbating the biogenesis of β-amyloid plaques in Alzheimer's disease. I had expected the insulin sensitizers to decrease β-amyloid, but the insulin sensitizer actually has a deleterious effect on Aβ. This may be due to the effect of the insulin sensitizer either on the insulin signaling pathway of the uptake of glucose through the glucose transporter.  

Future experimentation may further elucidate the "Spicy Situation" caused when cinnamon and other insulin sensitizers upregulate β-amyloid in Alzheimer's disease.