From USA Today

Harvard researchers unveil new Alzheimer's theory

http://usat.ly/1THTXLV

Researchers at Harvard this week offered a new theory of Alzheimer's Disease that - if true - would upend our understanding of the disease and suggest new routes for treatment and prevention. The researchers think that the immune system may play a key role in the development of Alzheimer's, which slowly robs people of their memory and is eventually fatal. A protein called beta amyloid, long considered the bad actor in Alzheimer's, actually plays a positive role in fighting off bacteria and fungus in  mice, worms and cells, the researchers showed in a new paper in Science Translational Medicine. Assuming that is true in people, it suggests that getting rid of amyloid, as some drug trials have tried, could be dangerous, and approaches that stimulate the immune system could be safer and more effective.

Welcome, Caroline and welcome back Serenoa and scma.  

Hyperinsulinemia and certain chronic bacteria, viral, and fungal infections activate a type of receptor (receptor tyrosine kinase) that can lead to Alzheimer's disease.  Glucose in the brain is converted into myo-inositol which eventually leads to the formation of amyloid and peroxynitrite--ONOO-  (via receptor tyrosine kinases among others). Pre-diabetes and Type 2 diabetes leads to more glucose in the brain which increases the risk for Alzheimer's disease.

The following links provide the pathway to Alzheimer's disease.

http://d3b065mnuq5ztn.cloudfront.net/content/ppbiost/32/5/799/F2.large.jpg

http://web.pkusz.edu.cn/ouyang/files/2013/04/Signaling-pathways.jpg

http://www.frontiersin.org/files/Articles/131867/fncel-09-00091-HTML/image_m/fncel-09-00091-g003.jpg

From putting pictures to the words to putting words to the pictures.

Myo-Inositol, N-Acetylaspartate Are Sensitive Biomarkers for Conversion From MCI to Alzheimer's Disease

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.

A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta(25-35).

The amyloid precursor protein and amyloid oligomers activate protein kinase C via g protein coupled receptors (amyloid plaques apparently do not).  If protein kinase C is not activated there is no peroxynitrite and there is no Alzheimer's disease.  If peroxynitrite is adequately scavenged, there is no Alzheimer's disease.  If peroxynitrite is scavenged and its nitro-oxidative damage is partially reversed there is a partial reversal of Alzheimer's disease (by panax ginseng, cbd oil, and aromatherapy with essential oils high in eugenol, for instance).

As a side note peroxynitrite is part of the immune response against pathogens but it often does more damage to the brain than to the pathogen.  Peroxynitrite can also eventually dampen immune responses.  Pathogens are just one of many factors that can trigger the pathways that lead to Alzheimer's disease; others include environmental toxins, certain medications (such as chronic acetaminophen use and bisphosponate osteoporosis drugs), genes, an unhealthy diet (too much consumption of sugar, carbohydrates, salt, etc.), and psychological stress.

Serenoa, thank you for mentioning the interview. Yes, I agree. More evidence is coming out that implicates  inflammation and immune system response as being the culprits. And now it could be infection.

Here's the interview in Science Friday of Dr Moir and Dr Tanzi.

           Could Brain Infection Set the Stage for Alzheimer’s?
            http://www.sciencefriday.com/segments/could-brain-infection-set-the-stage-for-alzheimers/

There are many dissenters on the prevailing plaques and tangles hypotheses as being the cause of AD. But sadly, even the latest clinical trials are still targeting amyloid beta.

I posted an article before on Dr George Perry, an outlier in the AD research who believe that oxidative stress plays a major role. He observed that when inflammation is up, the amyloid beta is down, and when inflammation is down, amyloid beta is up. That they are related.

Here's a recent article where he discussed his work on oxidative stress.  

   Prof George Perry: Perspectives on Alzheimer’s Disease Research – Part 1
   Key role for oxidative stress
    http://www.selectscience.net/editorial-articles/prof-george-perry-perspectives-on-alzheimers-disease-research--part-1/?artID=39817

   Prof George Perry: Perspectives on Alzheimer’s Disease Research – Part 2
   Are amyloid plaques the best therapeutic target?
   http://www.selectscience.net/editorial-articles/prof-george-perry-perspectives-on-alzheimers-disease-research--part-2/?artID=39829

There are members in our Message Board who are proving healthy lifestyle changes can make a big difference in slowing down AD. They reaffirm the lifestyle intervention studies.  

Thank you for the valuable information, scma.  Factors that increase nitro-oxidative stress (pathogens, an unhealthy diet, environmental toxins, etc.) initially overactivate the immune system but can eventually down-regulate the immune system.

http://www.jimmunol.org/content/162/6/3356.full.html

 https://scicasts.com/neuroscience/2041-neurodegeneration/10166-mobilizing-the-body-s-own-immune-cells-to-help-fight-alzheimer-s-disease/  (although since amyloid plaques are not likely a cause of Alzheimer's disease trying to activate the body's immune system against amyloid plaques is likely to be at best unsuccessful and at worst counter-productive).

Hi, I've got some other research:

author Dale Bredesen, MD, a professor at the Buck Institute and professor at the Easton Laboratories for Neurodegenerative Disease Research at UCLA

"Small trial from the Buck Institute and UCLA succeeds using systems approach to memory disorders"

(key words: small trial - it still must be analysed and tested)

http://www.buckinstitute.org/buck-news/reversal-memory-loss-ad

Dale Bredesen discusses the metabolic factors underlying Alzheimer’s Disease

https://youtu.be/HS7VZydS8HI?t=3m51s

Thanks for posting this Tom(ek).  I am going to get lazy and post my response from another website.

My concern with this protocol is twofold: one is the sheer number of interventions which makes compliance difficult and two would it be helpful for someone in the middle to later stages of the disease.

Alzheimer's is a disease caused by the oxidation and nitration of important receptors, enzymes, and transport systems in the brain. Certain interventions that may reduce that oxidation and nitration early on (such as certain anti-inflammatory drugs or supplements such as fish oil) may not help those later in the disease. A diet that reduces consumption of sugar, carbohydrates, and salt; and estrogen replacement therapy helps lower myo-inositol levels which are an important early biomarker for Alzheimer's disease. But as the disease progresses, myo-inositol levels drop except for in people with neuropsychiatric problems in Alzheimer's disease so this type of intervention may only help a certain subset of the population. On the other, estrogen replacement therapy can actually increases oxidative stress and the risk of Alzheimer's disease when given relatively late in life.

Reduction of stress (yoga, meditation, mild exercise, providing a comfortable environment, etc.), a diet high in polyphenols (a Mediterranean diet of a diet from India), and the use of antioxidant supplements are probably the key elements of the protocol that would help reduce the risk of Alzheimer's disease, lead to improvements early on, and slow down the progression of the disease later on.

Here is a partial list of some of the antioxidants used in the study:

curcumin, melatonin, vitamin D3, bacopa monniera, Aswagandha, coconut oil, resveratrol, coenzyme Q10, and methylcobalamin (Vitamin B12).