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Alzheimer's disease: Do we finally have it figured out?
Lane Simonian
Posted: Thursday, September 7, 2017 10:17 AM
Joined: 12/12/2011
Posts: 4854


Although I have been somewhat critical of Dr. Bredesen in the past, he is probably furthest along in understanding Alzheimer's disease.  The following quotes may seem outlandish to some, but there are not too far from current reality.

"Alzheimer's disease is no longer a mystery," he explains, "You don't have to say, 'We don't know why you get it. We don't know what to do about it. We do know why you get it. We do know what to do about it. And we know how to prevent it."

The key, he says, is early testing of Alzheimer's 36 causes and a personalized approach to deal with any shortcomings. Just like a roof with 36 holes can only work if all 36 are repaired, Dr. Bredesen says there are 36 causes of Alzheimer's that must all be addressed.  His treatment focuses on figuring out exactly why a person is experiencing cognitive decline and correcting those deficiencies. 

"If there are specific exposures, you want to get rid of those," he says. "If there are nutritional changes, you want to address those, if there are hormonal changes you want to address those, if there are inflammatory changes...address those."

So while genetics means an estimated 75 million American are predisposed to have Alzheimer's Disease, Dr. Dale Bredesen says they no longer have to fear being tested because now there is something they can do about it.  

The first important point is that there are multiple causes for Alzheimer's disease.  Amyloid oligomers are only one of them.  That is why removing oligomers even early in the disease has failed.

The following analogy is also helpful.

“It could be a bit like the Mississippi river,” says Dr Hardy. “You can start in all sorts of places, but eventually you’re going to end up in New Orleans.” If Alzheimer’s is a general response to all sorts of neurological triggers then it may be that the fungal infections found by Dr Carrasco are simply one of a long list of causes.

In essence anything that is toxic to the brain whether it be high levels of sugar, mercury, chronic smoking, amyloid oligomers or stress can cause Alzheimer's disease.

One approach is to identify the factors that lead to Alzheimer's disease and as much as possible remove those factors for each individual.  To a large extent that is a Bredesen approach.  Another way of treating Alzheimer's disease is to work further downstream. Protein kinase C is one of the first major check points:

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.

Aricept and other acetylcholinesterase inhibitors inhibit protein kinase C activation but not enough to alter the course of the disease.

As Alzheimer's disease progresses, protein kinase C activity decreases due to oxidation. Many of the factors Dr. Bredesen identifies as causes of Alzheimer's disease activate protein kinase C. As the disease progresses removing these factors is likely to make little difference in the treatment of the disease.

The next checkpoint in the progression of the disease is NMDA receptor activation.

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.

Namenda does not do a particularly good job in inhibiting NMDA receptor activation. Antioxidants such as eugenol in various essential oils via aromatherapy, cannabidiol in CBD oil, and ferulic acid, syringic acid, vanillic acid, p-coumaric acid, and maltol in panax ginseng do a much better job than namenda at inhibiting NMDA receptor activation.  They also remove oxidants and repair part of the damage they do to the brain.  THC in CBD oil and ferulic acid in panax ginseng also lower norepinephrine levels which help treat neuropyschiatric problems in Alzheimer's disease, frontotemporal lobe dementia, and dementia with Lewy bodies.

So Dr. Bredesen has not found the holy grail, but he is close.  After thirty years down a rabbit hole, maybe the time has finally come to peak up and see the sun.



Donr
Posted: Monday, September 18, 2017 4:38 AM
Joined: 4/6/2014
Posts: 572


I read an article by him last week. It was  very interesting and makes you think that some of the clinical trials that are going on are barking up the wrong tree.

My wife was diagnosed with MCI Alzheimer's related. For the next four years the Neuro Psy test showed  a slow decline in abilities. The last one taken this past June there was improvement in the test and she stopped following the downward trail.

Now going back to the year she was diagnosed, she came down with a serious infection in the hip. After many failures with targeted antibiotics to control the infection and the doctor wanted to try a broad span antibiotic , Bactrim, that over the next six months returned all her blood work back to  normal.  I read an article about a study done by,  I think the name, at Chicago University, that was testing broad band antibiotics and found promising results. She is still taking the antibiotic for her hip.

Don


Lane Simonian
Posted: Monday, September 18, 2017 2:58 PM
Joined: 12/12/2011
Posts: 4854


I am very glad that the antibiotic has helped your wife.  I do believe that bacterial infections can contribute to cognitive decline.

Some antibiotics not only reduce the oxidative response to bacteria, they are also antioxidants themselves.   These antibiotics may be helpful even during the late stages of Alzheimer's disease.

http://www.alzforum.org/webinars/pathogen-hypothesis (especially question and answer section).

http://www.uchospitals.edu/news/2016/20160721-alzheimers.html (thanks for the lead).

For some the problem with broad spectrum antibiotics is C. diff.  

I just finished reading Dr. Dale Bredesen's book this weekend.  I am a slow reader but the science was not too heavy and it was written in a very clear and accessible style.   I liked his focus on multiple causes and multiple treatments for cognitive impairment.