Today over half of Americans who reach 85 will get an Alzheimer’s disease diagnosis and in less than 25 years, the Alzheimer’s Disease incidence will triple to what it is today. In England, where holistic lifestyle has not been well rooted, Alzheimer’s Disease (heretofore AD) has replaced both cancer and cvd as the number one killer and the US is not far behind, in particular for the elderly. For those with the APOE 4 gene, the risk factors are higher and strike earlier. In order to better understand what health enthusiasts should do and what they should cease from doing, Part A of this book will first look at pathophysiology and etiology (pathogenesis or causation), in particular, the pathophysiological mechanisms that are related to the vasculature, oxidative stress, toxemia, neuro-inflammation, insulin resistance, genes, epigenetics, abnormal phosphorylation and the microbiota. Thereafter, once we have determined what the correct chain of causation is with regard to AD’s initiation and progression, the book will delve into Holistic neurology, the Institute’s Twelve Great Holistic Fundamentals, a specific brain-enhancement French Mediterranean inspired Lifestyle, quality wine, botanicals like rosemary and astralagus and other approaches. (Part B). The author of this book, Professor Joubert, is a biogerontologist who specializes in optimal healthy supercentenarian lifespans. He teaches all over the world the best available longevity techniques that are safe, efficient, accessible and cost-friendly.
For over 30 years, the primary focus for researchers studying Alzheimer disease has been centered on amyloid-beta, such that the amyloid cascade hypothesis has become the “null hypothesis.” Indeed, amyloid-beta is, by the current definition of the disease, a major player in pathophysiology, is toxic to neurons in vitro, and, perhaps most compelling, is increased by all of the human genetic influences on the disease. Therefore, targeting amyloid-beta, has understandingly been the focus of considerable financial, basic and therapeutic interest.
However, for over 20 years, the emerging evidence has suggested that an “alternate hypothesis” may be more fruitful, one that would postulate that while amyloid-beta, is still involved in the AD disease process, it is not an initiating event but rather is secondary to other pathogenic events, what can be called one of multiple symptoms. Furthermore and perhaps most contrary to current thinking, the alternate hypothesis proposes that the role of amyloid-beta is less as a harbinger of death than a protective response to neuronal dysfunction and toxemia that crosses the blood brain barrier.
In this perspective, current evidence and mounting Research suggest that conventional neurologists have wrongly postulated that the major culprit of AD is a symptom or group of symptoms that drives the disease. If conventional neurologists were correct in their analysis, AD drugs would show clinical progress. Yet, after over 30 years and billions of dollars testing drugs in clinical trials, not one of these anti amyloidal drugs made a difference in terms of safely and efficiently treating this disease.(Source)
While the amyloid plaque did shrink with some of these drugs, just like cytotoxic chemo can shrink tumors, there has been no established correlation between plaque shrinkage and AD survivability, just like in conventional oncology.
In this book study, I have analyzed this disorder holistically, focusing on the big picture beyond symptomatology. (Source)
What the mounting evidence suggests is that the amyloid plaque, just like the arterial and dental plaques, appear to be a defense mechanism against other deeper causes that conventional medicine has missed or underestimated. In effect, the relevant data demonstrates that beta amyloidosis arises in order to protect the brain against toxic proteins, heavy metals like mercury, copper, iron and even molds (mycotoxins). (Source).
For over twenty years now, we have known that the so called central “Alzheimer Disease hallmark”, the beta-amyloidal plaques is not the driver of the disease. Below, a 2004 piece from a group of scientists who are not fooled by conventional medicine’s approach.
“Ever since their initial description over a century ago, senile plaques and their major protein component, amyloid-beta, have been considered key contributors to the pathogenesis of Alzheimer disease. However, counter to the popular view that amyloid-beta represents an initiator of disease pathogenesis, we herein challenge dogma and propose that amyloid-beta occurs secondary to neuronal stress and, rather than causing cell death, functions as a protective adaptation to the disease. By analogy, individuals suffering from altitude sickness nearly always have elevated levels of hemoglobin. However, while hemoglobin is toxic to cells in culture and increased erythropoiesis at sea level can be deadly, it is clear that the increases in hemoglobin occurring at altitude are beneficial. Amyloid, like hemoglobin, may also be beneficial, in this case, following neuronal stress or disease. Although controversial, a protective function for amyloid-beta is supported by all of the available literature to date and also explains why many aged individuals, despite the presence of high numbers of senile plaques, show little or no cognitive decline. With this in mind, we suspect that current therapeutic efforts targeted toward lowering amyloid-beta production or removal of deposited amyloid-beta will only serve to exacerbate the disease process. (Ann N Y Acad Sci. 2004 Jun;1019:1-4). (Source) (1)
The analogy on altitude hemoglobin is well taken. Instead of understanding why hemoglobin rises in high altitudes (ie, as a compensatory mechanism for the decrease in atmospheric pressure, which means less cellular oxygenation), conventional neuroscience would propose drugs to combat this compensatory increase in hemoglobin, a chemical intervention that would necessarily lead to deleterious effects.
Below, another piece of published evidence from 2002, wherein the authors show that both amyloid-beta and tau, the major components of senile plaques and neurofibrillary tangles, are less the central mediators of the pathogenesis of Alzheimer disease than protectors from upstream biochemical events or assaults, including, but not limited to oxidative stress and toxemia.
“… in light of recent evidence, such “lesion-centric” approaches look to be inappropriate.In fact, rather than initiators of disease pathogenesis, the lesions occur consequent to oxidative stress and function as a primary line of antioxidant defense. (…) The notion that amyloid-beta and tau function as protective components brings into serious question the rationale of current therapeutic efforts targeted toward lesion removal”. Free Radic Biol Med. 2002 Nov 1;33(9):1194-9 (Source) (2)
The hard facts in effect show that in the case of Alzheimer’s disease, there is not a single therapeutic that exerts anything beyond a marginal, unsustained symptomatic effect, with little if any effect on disease progression. Worse, emerging evidence suggests, like in conventional oncology, that most of conventional AD medicine worsens the AD experience. Furthermore, in the past decade, hundreds of clinical trials have been conducted with regard to AD, at an aggregate cost of billions of dollars. Yet, none have led to meaningful medical interventions. (Source)
Holistic Neurology and Innovative Neuro-science
In contradistinction to conventional allopathic model, which is focused on finding drugs that will destroy some of AD’s symptomatology, in particular the tau proteins and beta-amyloids, holistic scientists are looking out of the conventional “box” and finding more significant events that are upstream of these amyloidal “senile” plaques. One of the key upstream factors is related to inflammation. A diet and lifestyle that does not chronically inflame the adrenal glands and microbiota helps to prevent this disease. In this perspective, recent research at the Brown University in Rhode Island showed that the development of Alzheimers is connected to lifestyle assaults, in particular to that which causes diabetes, the lack of insulin sensitivity. (Source) Among dozens of other integrative and holistic techniques, non-invasive brain stimulation have been demonstrated to be beneficial, in particular transcranial direct current stimulation (tDCS), a method of neuromodulation with consecutive robust excitability changes within the stimulated cortex area AD. These and dozens other techniques will be explored.
Discussion and Conclusion
If insanity is doing the same thing over and over again but expecting different results, then the last decade or so of Alzheimer’s disease drug development has been insane. Three carefully designed, well-executed, and fully resourced trials targeting amyloid protein in the brain as the cause of Alzheimer’s disease have been unsuccessful. (Source A) (Source B) (Source C) Each program was run by a pharmaceutical company with significant experience and unlimited access to expertise and the financial resources needed to ensure success. One failed program may be bad luck. Two might be explained away. But after three or four it doesn’t take a medical scientist with many letters after his or her name and decades of research experience to conclude that amyloid is not the cause of Alzheimer’s disease. Although these drug-development failures have been disappointing for individuals with Alzheimer’s and their family members, disproving the amyloid hypothesis may be a positive happening in that these failures could spur the transition from the old drug based paradigm to the more holistic based approach to medicine. Instead of biopharmaceutical groupthink, in which all companies pursue the same strategy, scientists and companies may want to step back, evaluate the data, and commit to innovative innovative programs. And so far, the best available approach to this mind-robbing disease is holistic.
In the Institute’s book, we show with an overwhelming preponderance of the evidence that Alzheimer’s Disease is a Lifestyle, nutritional, microbiota, oronasal and toxicity challenge that can be both prevented and reversed with Holistic savoir-faire. By focusing on the holistic approach, the immune system gets stronger and is better able to clear the body of amyloid proteins, just like it clears cancer, senescent and endometriosis cells as well as bacteria pathogens, in particular those that produce LPS and amyloid proteins.
The gut microbiota as the source of a large amount of amyloid, LPS, and other toxins necessarily contributes to systemic inflammation and disruption of physiological barriers, including the blood brain barrier. Bacteria and their metabolites can move from the gastrointestinal tract and the oronasal cavity to the CNS, especially in the elderly. Bacterial amyloids act as prion protein cross-seeding misfolding and enhancing native amyloid aggregation. Gut microbiota products prime microglia, enhancing inflammatory response in the CNS, which in turn results in pathologic microglial function, increased neurotoxicity and impaired amyloid clearance.
The fact that scientists have been able to reverse key symptoms of Alzheimer’s disease with only fecal transplants (source) is one of many other pieces of evidence that show that modern medicine and pharmaceutical companies have been wasting precious time and billions of dollars fighting amyloid and tau proteins while missing key immunological and microbiota pathways that promote Alzheimer’s disease and other neurological disorders.
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