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A good explanation for Alzheimer's disease
Lane Simonian
Posted: Sunday, November 11, 2018 9:58 AM
Joined: 12/12/2011
Posts: 5107

Over the years, some of the best explanations for Alzheimer's disease has come from non-scientists.  Here is a particularly good one:

  • Wullydavidson
I'm a non scientist who has reviewed research into non-communicable diseases, including Alzheimer's, for 30 years. Almost all are being caused by chronic, aberrant activation of the transcription factor, nuclear factor-kappa beta (NF-kB). This includes Alzheimer's. 

NF-kB has multiple functions, but a principal function is the control of intracellular pathogens that establish long term latency inside cells, such as those mentioned in the article. Such infections often contribute to damaging over activation of NF-kB, but are not essential for the initiation of the disease process. Many other environmental and lifestyle factors contribute, such as gut microbiota, pro-inflammatory 'western' diet, exposure to environmental chemicals and metals, lack of immune challenge in infancy, lack of vitamin D, sedentary lifestyle, food/chemical allergy/sensitivity/intolerance, chronic psychological stress etc. Important genetic factors include polymorphisms of the immune system, receptors and enzymes. 
The NF-kB driven immune response combats cellular infection by causing reactive oxygen species to be produced inside cells. These are damaging to microbes. It also downregulates the receptors used by microbes to enter cells. This can take the form of reduced expression, desensitization, or receptor blockade by 'antibodies'. In Alzheimer's, the acetylcholine NACH [nicotinic acetylcholine] and noradrenaline receptors are downregulated. These receptors are involved in learning, so chronic downregulation results in the earliest symptom of short term memory impairment. When this situation becomes chronic, cells die, leading to advanced disease symptoms. 

A more detailed discussion can be found on my blog

To add and amplify when Nuclear factor kappa B and NADPH oxidase are simultaneously over-activated in Alzheimer's disease you get the production of peroxynitrite.  

Through oxidation and nitration, peroxynitrite damages receptors that limit the release of neurotransmitters needed for the retrieval of short-term memories, sleep, mood, social recognition, and alertness and dampen the effect that growth factors have on receptors involved in the regeneration of neurons and synapses in the hippocampus.