Part 1: The Root Cause of Alzheimer's disease: AD is not a neurological disease, but an immune-based disease with neurological symptoms.
Our research lab focuses on the assumption that Alzheimer's (AD) itself is not a neurological disease. Now you are probably thinking to yourself, wait that doesn't sound quite right at all-- but let me clarify this statement a bit. As it currently stands, most neurological diseases don't have associated cures. Most neurological diseases only have symptomatic treatment or invasive procedures to try and correct the pathologies or reverse the damage. If we think of Alzheimer's as a neurological disease, there is not much hope in terms of how we go about treating it, because it is simply just another one of those stubborn, incurable things in the medical field, or so it seems now. Alzheimer's, Parkinson's, ALS, un-vaccinated cases of polio, the list goes on. In all these cases, there are substantial changes to the nervous system. These changes develop over time, and though maybe there might be potential for reversal in the future with stem cell therapy, as it stands for probably the next 5-10 years, these changes cannot be reversed once they have taken place. The nervous cells and most of the nervous system (comprised of the central, CNS, and peripheral, PNS, systems) do not regrow most of the cells after they have already developed. So the focus of research needs to be on timely identification that these changes are taking place or going to take place and to stop any future change from occurring.
The first thing we need to do is think about what changes are taking place. The pathology of AD deals with amyloid beta (Abeta) aggregation outside of the nerve cell, and tau tangles inside the cell. The intracellular tangles disrupt the transport of cell signals along the inside of the axon of the nerve, and Abeta proteins outside the cell aggregate to disrupt cell-to-cell signalling. The field of research has been split on whether Abeta starts fits and tangles follow, or if tangles start first and Abeta follows. A very chicken and egg type of disagreement. Though both hypotheses have their merits, it is our belief that Abeta is first to develop, as single units, or monomers, can be found within the brain and blood at any age. When Abeta starts to aggregate, it puts stress on the cell and nervous environment, which then causes the tau tangles, the mitochondrial stress, and all other molecular incidences and pathologies of AD. If we can inhibit or reduce the Abeta production with age, we can probably delay the onset and hopefully decrease the incidence of disease within the elderly population.
So the question is, what happens between being young and becoming older where these natural proteins suddenly begin to build up inside the brain? Our hypothesis is that it relates to good immune homeostasis and balance. With aging, there is a slowing of the metabolism. Metabolism relates to all processes and chemical reactions that upkeep the cell, including the creation of any necessary molecules and the breakdown of any unnecessary molecules. Abeta falls into the second category. As of now, there is no known function of this short peptide. Initially, it is a part of a longer protein residing inside the cell membrane at the connection between 2 cells, but after this larger protein is cleaved, the function of the released Abeta is unknown. It is normally cleared from the brain when we sleep, through the glymphatic system, and it can also be broken down by a series of enzymes. The slowing molecular metabolism with age can allow for Abeta aggregation. However, we can't seem to find a way to improve metabolism without proper diet, drink enough water, and get enough exercise. There are no drugs or therapies that have been proven to boost all sites of molecular metabolism at the cellular and enzymatic levels. So one of the two ways of getting rid of these amyloid beta proteins is unlikely. The other way, through the glymphatic system, is feasible. The glymphatic system is an extension of the lymphatic system which crosses the blood-brain barrier and allows toxins to be cleared from the brain. These two interconnected systems are vital part of the immune system. With proper immune balance, we can avoid the overactivation of T-cells and B-cells, which then trigger an immune response to these Abeta oligomers which are seen as foreign to the body. Think of all the symptoms you have when you get a cut and it gets infected, it is essentially the same thing but it is on a smaller scale and occurring inside the brain. The inflammation and inflammatory factors promote swelling and the recruitment of immune cells to try and clear this aggregated peptide. What happens is that a miniature battlefield breaks out in between nervous cells, and the after effects is the eventual cell death. In any other part of the body this is okay, sacrifice some for the good of the whole, and it is fine because skin cells and epithelial cells in the gut will all grow back and repair itself. This is not the case with the brain and nervous cells. So some of the keys are to (1) notify immune cells that there is something different (aggregated Abeta) without mounting a full scale immune response as it would to a foreign pathogen, and (2) targeting key cellular relationships within complex immune system to lead to clearance of Abeta from the brain before inflammation and T-cell infiltration take place and we can no longer reverse the effects. It is also important to realize that these assumptions can only be acted upon within a balanced or relatively healthy immune system. If we try to take action with the aged, imbalanced system of an elderly patient, we will not get the accurate level of response we may need to clear enough Abeta continually from the brain. These are the hypotheses we are currently researching, with our various mutations of the Abeta peptide, to get an appropriate level of response, and with our dendritc cell (DC) vaccines, to target these key cellular relationships. We are the first lab group to try and redefine AD as an immunological disease with neurological symptoms. We will continue to explore this idea and the potential therapies these present. Through this route, we believe there is still hope for some type of treatment to delay or stop the development of Alzheimer's.
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This will become a continual series related to our current research, publications, and data and the various ideas we have related to the Alzheimer's research field.