Alzheimer's Disease: Putting Together the Puzzle

For the past year, visiting my grandfather has been a drastically different experience than what it was when I was younger. Coming up on three years, my grandfather was diagnosed with Alzheimer’s Disease. Upon arriving at the nursing home in Detroit Lakes, I am informed about my grandfather’s daily status. One day he is back in North Korea, the next he is getting ready for work, and another day he is playing cards with me and asking how college is going. As for anyone in this situation, it is very hard seeing someone you love’s behavior change so drastically without his or her conscious effort being a factor. This past week in my Neurochemistry class, we discussed implications of AD and other contributing factors that aid in the behaviors we see in AD.
Alzheimer’s Disease (AD) is the most common form of dementia that introduces problems with memory, thinking and behavior with those who are diagnosed with the disease. Although its prevalence in modern-day research is abundant, the recognition of AD as a disease with multiple pathological contributions within a dynamic whole is imperative to improving treatment. A singular dimension approach to prevention and therapy has been relatively ineffective in the realm of AD. Another pathological contribution to AD, insulin in biological systems, is the leading candidate in showing significant correlations with AD pathology.
During the past decades, higher life expectancies and altered eating habits has led to a correlation to the increase in the prevalence of age-associated diseases such as type 2 diabetes (T2DM). Insulin metabolism is one of the most critical regulators of longevity and aging. Recent studies have shown that insulin resistance in the central nervous system (CNS) is observed in both T2DM and AD. Insulin’s primary role in our bodies is the regulation glucose by promoting glucose uptake in muscle and fat. Historically, insulin is usually solely associated with T2DM, but recent evidence has shown that insulin plays a more extensive role in a range of physiological processes, cellular effects, and in relevance, serving a neuroprotective role in regulation of learning and memory.
The two main hallmarks of AD are two neuropathological processes; excess tau hyperphosphorylation and the over-production of amyloid-β (Aβ). In short, the result of an accumulation of these two compounds disturbs the neurochemistry of individuals with AD. Consequences include neurofibrillary tangles and other abnormal cholinergic factors that forfeit normal brain function due to the excess tau proteins and Aβ sterically disrupting the brain. Insulin resistance has demonstrated a relationship to these two biological explanations for the behaviors we see in AD. Normally, insulin activates a pathway called P13K/AKT which regulates tau phosphorylation and keeps Aβ levels in check. When an individual becomes resistant to insulin, whether it be obesity or aging, impaired P13K/AKT signaling results in the progressive accumulation of the hallmarks of AD. From this one can attribute the involvement of another molecular mechanism contributing to AD progression and insulin resistance.

Becoming a routine, the first question I ask my grandfather’s nurse, “How is his blood sugar doing today?” Prior to the exploration of this topic, the asking of this question was only attributed to the observations my family has made with the state of my grandpa’s behavior. High blood sugar levels—he’s back in North Korea, normal levels—he is the grandpa I have always known. My grandpa was not diagnosed with type 2 diabetes until a year after being diagnosed with AD. We were told that it appearance of both was more than likely due to aging exclusively. Understanding the mechanism behind the link AD and insulin resistance has given me a detailed insight into my grandpa’s diagnosis. Further understanding within AD and its implications is crucial to developing a better solution to alleviating symptoms seen in AD. Hopefully, modern medicine will allow us to address this issue and allow more people to visit their grandparents to play cards and not be told that their age related diseases are each explicitly due to their age.