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The gut, the brain, and Alzheimer's disease
Lane Simonian
Posted: Sunday, September 24, 2017 11:28 AM
Joined: 12/12/2011
Posts: 5158

Once or twice a year, an article comes out on Alzheimer's disease that helps provide a fresh perspective on the disease.  One of the ways that the pathogens and toxins that contribute to Alzheimer's disease enter the brain is through the nose, but the authors of this article make a strong case that another way these pathogens and toxins enter the brain is through the gut.

Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer’s disease (AD) and Parkinson’s disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g., superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation. NO also instigates a down-regulated secretion of brain-derived neurotrophic factor, which is essential for neuronal survival, development and differentiation, synaptogenesis, and learning and memory. 

Hydrogen peroxide (early on) and peroxynitrite are likely the two central oxidants in Alzheimer's disease.

"The gut–brain axis denotes communication between the enteric nervous system (ENS) of the GI tract and the central nervous system (CNS) of the brain, and the modes of communication include the vagus nerve, passive diffusion and carrier by oxyhemoglobin. Amyloid precursor protein that forms amyloid beta plaques in AD is normally expressed in the ENS by gut bacteria, but when amyloid beta accumulates, it compromises CNS functions. Escherichia coli and Salmonella enterica are among the many bacterial strains that express and secrete amyloid proteins and contribute to AD pathogenesis. Gut microbiota is essential for regulating microglia maturation and activation, and activated microglia secrete significant amounts of iNOS."

Bacteria, gluten, and pesticides and herbicides can all increase hydrogen peroxide and peroxynitrite formation in the gut (via g protein-coupled receptor--protein kinase C--NMDA receptor activation) and apparently these compounds can make their way into the brain.

Protein kinase C activation leads to the secretion of the amyloid precursor protein and early in Alzheimer's disease via NMDA receptors it leads to nitro-oxidative stress which is likely the main cause of Alzheimer's disease (protein kinase C activity decreases as the disease continues due to oxidation but high levels of glutamate continue to ensure perpetual NMDA activation as the disease continues).

"Malinow’s team found that when mice are missing the PKC alpha gene, neurons functioned normally, even when amyloid beta was present. Then, when they restored PKC alpha, amyloid beta once again impaired neuronal function. In other words, amyloid beta doesn’t inhibit brain function unless PKC alpha is active."

"We suggest that oxidative stress mediated through NMDAR and their interaction with other molecules might be a driving force for tau hyperphosphorylation and synapse dysfunction. Thus, understanding the oxidative stress mechanism and degenerating synapses is crucial for the development of therapeutic strategies designed to prevent AD pathogenesis."

The authors recommend the following:

Pharmacological interventions and lifestyle modifications to rectify aberrant NO signaling in AD include NOS inhibitors, NMDA receptor antagonists, potassium channel modulators, probiotics, diet, and exercise.

As a couple of side notes, Gene Wilder died from Alzheimer's disease and non-Hodgkins lymphoma--diseases in which peroxynitrite play a predominant role.

I have a Celiac-like disease likely caused by the use of the herbicide Roundup on wheat and other crops (polyethoxylated tallow amine in Roundup increases the formation of peroxynitrite).  It is interesting that Dr. Bredesen does not recommend probiotics until you test to seek if a leaky gut has been healed.  I am not sure yet how sound this advice is.

I am mixing up words when I write these days.  The long and short of it is that if you have a leaky gut you can end up with a leaky brain.


Lane Simonian
Posted: Sunday, September 24, 2017 7:11 PM
Joined: 12/12/2011
Posts: 5158

Along the same lines (although oxidation is a more persistent problem than inflammation in many neurodegenerative diseases:

The Gut and Brain Commection

Neurotoxic insults start the chain of reactions (heavy metals, nutritional deficiencies, viruses/fungus/bacteria, inflammatory diet, MSG, solvents, pesticides, herbicides, etc.): one or more of these factors destabilize the tight junctions of the blood brain barrier, which leads to neurogenic inflammation. The result is Parkinson’s disease, MS, dementia, chronic pain, behavioral and personality changes, Alzheimer’s disease, ALS and Lyme disease.

Inflammation can start in the gut, lead to leaky gut syndrome and break down the blood/brain barrier. The end result is that the brain also gets inflamed and Alzheimer’s disease and dementia can occur. The sooner treatment is begun, the faster the recovery will be. When the end stage is reached, it is difficult to turn the inflammatory process around. Fortunately there are effective ways to get the inflammation under control with intravenous glutathione in the beginning and subsequent treatment with lipidated curcumin, omega-3 fatty acid and vitamin D3. A permanent switch to a Mediterranean diet is important as well to keep inflammation under control.

A few years back this type of approach would have been considered as “quackery”; now it is the latest information from research into the brain/gut connection. A lot can be done on a preventative basis with lifestyle and nutrition choices. Treatment is possible, but once full-fledged disease is established, a full cure may not be possible.

Posted: Saturday, September 30, 2017 11:05 PM
Joined: 12/17/2015
Posts: 32

You have a lot of interesting observations and things to make people aware. I am considered a pretty smart person, as I am told, but I wish I could understand what you are talking about. It is so hard to decipher. I have read about about your suggestions for aromatherapy and have used some for my husband. I also read about your ideas on polyphenols and almost had my husband join a study for grape seed extract given in very high doses. The protocols for the study were poorly thought out. Please try to write in direct language because your ideas are very good and helpful. Right now I have to read between the lines to understand.
Lane Simonian
Posted: Sunday, October 1, 2017 9:32 AM
Joined: 12/12/2011
Posts: 5158

The processes of this disease are hard to describe in simple terms, but here is the essence.

Peroxynitrite is a compound that damages both the gut and the brain.  Various toxins including bacteria, viruses, and environmental contaminants increase the formation of peroxynitrite.  These toxins can reach the brain via several different routes including the nose and the gut.

Compounds that get rid of peroxynitrite such as essential oils via aromatherapy, panax ginseng, grape seed extract and other polyphenols, medicinal marijuana, and gluthatione produced by some beneficial bacteria also reverse some of the damage done to the brain by peroxynitrite.  This is why these substances have the best chance to partially reverse Alzheimer's disease.