Imagine waking up in the morning and seeing the snow hit the ground. But…. Isn’t it July? I remember having plans with uncle Tom to go fishing this afternoon… Whats going on?
This is a bit of an extreme example of what an Alzheimer’s patient may think about when dementia sets in, however, it is a very real aspect that most Alzheimer’s patients go through. What is even tougher to understand is the complexity of this disease and all the factors that play a role in developing Alzheimer’s. From genetics to environmental exposures, Alzheimer’s disease is incredibly scary.
When looking closely at Alzheimer’s, there are a lot of biological cues that can lead to diagnosis. Accumulation of tau proteins (neurofibrillary tangles) and amyloid-beta plaques (AB-42) is found in a majority of cases, followed with neurodegeneration of the entire brain. Essentially, this accumulation of AB-42 was thought to be an over production of the amyloid precursor protein (APP), but recent studies have shown that the production of APP is still normal, and it is in fact the removal of AB-42 in the body that has slowed down. How AB-42 is made in the first place is a simple enzymatic error occurring during enzyme cleaving (normal cleaving gives AB-40).
Why this error is occurring in some individuals more than others is due to a gene mutation of PSEN-1, PSEN-2, or APPG. These genes encode the formation of the APP protein, and when a mutation occurs, the APP protein is synthesized incorrectly. This allows improper cleaving to occur more often, and AB-42 plaques to build up faster, and more recently. However, not all of Alzheimer’s disease is caused genetically.
In a majority of Alzheimer’s patients, it is found that a upregulated signaling of the mTOR pathway of neurons is causing a systematic overload within the endoplasmic reticulum (ER) to occur, thus leading to cell atrophy (neurodegeneration). Essentially, the ligand that upregulates this pathway, is the combination of TNF-alpha and insulin. Alzheimer brains are found to be more insulin resistant, which may result in no counteraction against TNF binding, assuming that insulin binding effects the binding affinity or ability of anterograde signaling for TNF. When this over abundance of TNF binding is occurring, protein synthesis in the ER is sent into overdrive. This induces an inflammatory response within the neuron, which will likely cause cell death.
Because of insulin’s involvement in the brain and this particular instance, diet and exercise play a key role in staving off Alzheimer’s and possibly even preventing it. Future research is also looking into the importance of being type-2 Diabetic and how that can play as a risk factor in the disease too. At this point in time, there is just too much involved with Alzheimer’s disease that some make the argument “it’s just aging”. Although this statement is some what true, with a majority of diagnosed individuals being over the age of 65, I myself would still like to believe that we should all be able to grow old and die someday, without losing our mind both physically and psychologically.