Neurons let us sense and see our world, move our muscles, and think and remember. The APP beta-amyloid precursor protein is produced in neurons throughout the body. Too much cutting of the APP protein releases too many beta-amyloid peptides and is a major cause of neuron degenerative disease in humans. Neurodegenerative disease decreases our ability to sense and see our world, move our muscles, and perhaps most importantly: blocks our ability to think and remember (Alzheimer’ disease).
Beta-amyloids can be produced anywhere in the body. They are generated when the beta-amyloid precursor protein (APP) found in synaptic vesicle membranes in neurons is “cut” by other proteins into separate, smaller sections (peptides). Beta-amyloid peptides derived from APP have important well-defined roles in neuron degenerative disease. Thus, they are considered keys to neuron disease.
Aging and diabetes are major factors in Alzheimer’s disease and all three are linked by increased beta-amyloid peptide production. Beta-amyloid peptide solubility and amount of beta-amyloid self-association (oligomer formation) determines the role of beta-amyloid in disease. It is clear that APP beta-amyloid precursor protein gene mutations that increase beta-amyloid production lead to devastating early-onset Alzheimer’s disease.
A certain small percentage of Icelandic population essentially does not “get” Alzheimer’s disease” due to genetic mutation in APP (Callaway, 2012). This newly discovered APP gene mutation is unique such that it decreases beta-amyloid in these individuals. Additional researches showed that beta-amyloid solubility, quantity, and composition are key factors that determine its role in the disease process and its clinical manifestation (Murphy & LeVine, 2010). These studies highlight the importance of beta-amyloid levels and different beta-amyloid forms in Alzheimer's disease mechanisms.
Innovative mouse studies also demonstrate the critical role of beta-amyloid in the circulation in Alzheimer’s disease.
The mouse is a mammal that normally cannot “get” Alzheimer’s disease because mice normally produce beta-amyloid peptides whose composition differs from the human beta-amyloid. With this stated fact, a study was conducted (Bu et al., 2017), wherein the bloodstream of a mouse genetically engineered to produce “human-like” disease-causing beta-amyloid peptides was connected to the bloodstream of a normal mouse. As a result, the normal mouse “got” human beta-amyloid Alzheimer brain disease. This means that disease-causing “human” beta-amyloid peptides were able to travel from the genetically modified mouse into the normal mouse brain and produced Alzheimer beta-amyloid pathology including plaques. This further demonstrates the critical role of beta-amyloid in the circulation in Alzheimer’s disease.
Normally, the body keeps beta-amyloid at low manageable levels, but these processes become dysfunctional as the body (and brain) ages (Weller et al., 2008). When beta-amyloid accumulates, it “clumps” easier and forms plaque deposits. Increased beta-amyloid is causally linked with neuron degenerative disease in the brain (Alzheimer’s disease) but also in neurons elsewhere in the body. Beta-amyloid over-production occurs at neuron-muscle junctions in muscle fibers in the major human muscle degenerative disease (Greenberg, 2010): inclusion body myositis (IBM), and in the retina in diabetic retinopathy (Ratnayaka, et al, 2015) (most retina cells are neurons!).
Furthermore, beta-amyloids produced in the brain and throughout body are normally prevented from freely passing into the brain due to the “blood-brain-barrier” separating the brain and its blood system from the rest of the body. However, as we age, this barrier breaks down and allows beta-amyloid peptides to more easily move into (or out of) the brain. (Haridy, 2017). This means beta-amyloids from the circulation can easily enter the brain and add to the brain beta-amyloid load, thereby increasing formation of beta amyloid oligomers and brain plaques which have been classic markers of Alzheimer’s disease (Sadigh-Eteghad S. et al, 2015).
The human aging process is also influenced by metabolic disorders that include impaired blood glucose control and brain trauma. As a result, the formation and disposal of beta-amyloids in the brain is no longer efficient. This increases accumulation of beta-amyloids and plaque formation in the brain (ibid).
Considerable evidence identifies a close link between Type 2 diabetes and Alzheimer's disease (Akter et al, 2011). Similar to the aging process, high blood glucose is closely associated with oxidative stress, a key component of Alzheimer’s disease. Diabetes links with retina degeneration (known as diabetic retinopathy, DR) have been clear for many decades. DR is also a major cause of blindness worldwide. Moreover, studies show that Type II diabetics have a 60% increased risk of developing Alzheimer’s disease and accelerated cognitive decline (Vagelatos & Eslick, 2013).
Globally, over 400 million people have diabetes (WHO, 2016). In the United States, about 30 million are diabetics (CDC, 2017), wherein 90% have Type II aka “adult-onset diabetes”. Type II diabetes has increased at a staggering rate over the past 30 years and is expected to increase again by 50% by 2050 . In relation to the eye, study results demonstrated that the overall prevalence of any DR (in Type I and II diabetes) was 34.6%, with 7% vision-threatening DR (Yau et al, 2012). Otherwise stated, studies from individuals with diabetes showed that they had developed diabetic retinopathy and vision loss.
This information suggests that patients with type II diabetes are at high risks of developing Alzheimer’s disease in addition to the DR they will more likely develop due to diabetes. They have high chances of losing both their memory and their vision. Also, troubling, many individuals are unaware that they are already at the early stages of diabetes.
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Vagelatos, N. & Eslick, G. (2013). Type 2 Diabetes as a Risk Factor for Alzheimer’s Disease: The Confounders, Interactions, and Neuropathology Associated with This Relationship. Epidemiologic Reviews 3(1), Pages 152–160. Retrieved from: https://doi.org/
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