Dementia is the umbrella in which several neurodegenerative diseases fall under. Some of them include Parkinson's, Huntington's, frontotemporal dementia, mixed dementia, lewy body dementia, and vascular dementia. The most common form of dementia is Alzheimer's Disease (AD) and affects millions of people all over the world and is currently a growing and expensive problem. Extensive research has been done to try and combat the neurobiological effects leading up to and caused by the disease, but many theories are inconclusive. This project will narrow its focus on Alzheimer's disease and its pathological features.
Alzheimer's Disease is typically characterized as a progressive disease denoted by 7 stages. In the rare, early-onset AD, the first of these stages can begin as early as your 30's. But most patients are of late-on onset AD and start to see symptoms in their 60's. The first four stages of Alzheimer's disease deal with progressive decline in brain chemistry and basic cognition. This affects memory in all aspects of life: memory retrieval, word associations, organization difficulties, etc. The fifth stage introduces emotional changes and a greater decline in their ability to complete every-day activities independently. Some patients can begin to have hallucinations, paranoia and can struggle immensely to learn new things. The sixth stage is where patients start to experience much more severe symptoms like the inability to communicate, noticeable personality changes, increased anxiety with unfamiliar experiences, and trouble recognizing relationships. The seventh stage is where the most severe decline in motor function is experienced; patients will have trouble walking, eating and are more prone to other diseases because of their forced sedentary lifestyle.
The video to the right mentions some of the main biological, chemical and functional changes to the brain associated with Alzheimer's disease. Some of which are the formation of beta-amyloid (βA) plaques, the formation of neurofibrillary tangles (NFTs), vascular system dysfunction, glucose metabolism dysfunction, and chronic inflammation. The interconnectedness of each one of these presuppositions is, for the most part, indefinite. Although, as standalone indications of Alzheimer''s, the formation of βA plaques and NFTs have sufficient research behind them to conclude their necessity to the disease.
What role does microglia play in the breakdown of beta-amyloid plaques?
What are current pharmaceutical modalities available to slow the progression of AD?
How does phosphorylated tau self-assemble? In what conditions does this occur?
What is the relationship between beta-amyloid and phosphorylated tau?
Alzheimer's is a treatable disease. We are slowly making breakthroughs in the field of drug development to slow its progression, but these developments are nowhere near where we need them to be because we are yet to call Alzheimer's curable. While there is a great amount of information known about the biological mechanisms involved in the pathology of AD, there is likely a greater amount that we do not know. There is very little known about the function of beta-amyloid in a healthy brain. There is very little known about the presence of phosphorylated tau in a healthy brain. Even though we know there is a correlation between the two proteins, it is undefined how dependent the formation of hyperphosphorylated tau is on the presence of beta-amyloid. There are virtually no experimental articles that explore or test the relationship in the current library of data. The last several decades have come with great advancements for the scientific community, but we still have a long way to go.
Alzheimer's Disease Facts and Figures. Alzheimer's Disease and Dementia. (n.d.). https://www.alz.org/alzheimers-dementia/facts-figures#:~:text=More%20than%206%20million%20Americans%20of%20all%20ages%20have%20Alzheimer%27s,older%20(10.7%25)%20has%20Alzheimer%27s
How Alzheimer's Changes the Brain. Youtube, National Institute on Aging, 23 August 2017, https://www.youtube.com/watch?v=0GXv3mHs9AU.
The 7 Stages of Alzheimer's Disease. Pennmedicine.org. (n.d.). Retrieved March 22, 2023, from https://www.pennmedicine.org/updates/blogs/neuroscience-blog/2019/november/stages-of-alzheimers