ALZHEIMER’S DISEASE Part 2

WHAT IS NEW WITH THIS THIEF OF OUR MIND?  WHAT IS ALZHEIMER’S DISEASE IN A DISH?        

I believe the scientific community is close to solve the secrets of this puzzling and devastating disease.

Prominent Neuroscientist Dr. Kenneth S. Kosik from the University of California, a Professor of Neuroscience Research and has helped to discover the tangles of tau protein in the brain that are considered important hallmark of AD, in his recent and very instructive article, [Scientific American (May 2020)], states that “our inability to come up with a good treatment means it is time to re-examine the basic biology of the disease.  Alzheimer’s, in its core, is a problem in nerve cell biology. Therefore, concentrating on scientific work that has been driven by a central assumption that protein fragment, called beta-amyloid, plays central role in the disease is misguided. Because, we have developed drugs that reduce the concentration of these protein fragments in the brain, yet these drugs have not stopped patients’ steady cognitive declines.”

Since Neuroscientists agree that Alzheimer’s Disease (AD) in its core is a neuro-degenerative disease of brain cells, then it only makes sense to study the disease process at the human brain’s nerve-cells (neurons) level.

For this, since doing a brain biopsy is not feasible, brain nerve cells must be obtained from a skin biopsy. They are then cultured and produced in a petri-dish, from genetically prone, early-onset AD candidate patients by using IPSC (Induced Pluripotent Stem Cell) technology. This has been accomplished by many brain science research laboratories on worldwide basis. Among them, Harvard’s stem-cell scientists have successfully converted skin biopsy cells from patients with early – onset Alzheimer’s into types of neurons that would be affected by the disease, making it possible to study the pathophysiology of “Alzheimer’s Disease in-a-Dish.”

Since the initial development of Alzheimer’s Disease in-a-dish, more enhancements have been made in cell culture media that provide the development of tau proteins, tangles and neuro-inflammations in a petri dish - the three main components of Alzheimer’s disease. This makes it possible to study AD at cellular and molecular level and test many drugs for prevention and treatment purposes.

At this stage, I would like to raise some questions of my own. If AD is caused by distorted brain nerve cells biology and brain cells deaths, why then are only certain memory cells are involved?  Why does music memory and music appreciation remain intact? I remember my in-laws’ faces light up when I played a folk song called, “Sulico” from their old country Russia and they start singing along.

Among risk factors, getting older is the biggest risk factor for Alzheimer’s Disease. 50% of AD cases are seen after the age 80. Could it be that AD is a natural phenomenon of aging, just like we lose our hearing or our sharp vision when we get old? Maybe our memory cells too are preprogramed to die earlier than our unusually prolonged lifespan by modern medicine. Maybe Nature and Evolution didn’t know we would be living this long?

A recent informative article, in the May 2021 issue of Scientific American journal by D. Kaufer and A. Friedman presents evidence that under various environmental risks factors, like extreme stress and aging, cause leaks of protein to occur in the protective vascular filter called the brain – blood barrier (BBB). These leaks, especially the albumin protein leak, may lead to AD and other dementias. Animal experiments showed that reversing these leaks makes aging animals brains and their behaviors look younger and healthy.

Being female is the second biggest risk factor for AD, why?

Researchers believe that the estrogen hormone is major regulator of brain cell biology and metabolism, from glucose transport and uptake to its breakdown for energy. There is a 20-30 percent drop in brain glucose metabolism after menopause. The brain compensates by tapping into other sources of energy (like lipids and protein), which makes brain cells vulnerable to damages.

Many experts agree that fine particle air pollution, called MP2, is another big risk factor. It is caused by exhaust particles from burning oil and gas in cars and trucks and power plants, to also burning coal and wood. These particles are so small that they are easily inhaled while breathing and pass from the lungs into the blood circulation and then pass blood-brain barrier into the brain cells. These particles cause brain’s immune cells (microglia) to release cytokines and induce defensive inflammatory reaction. Chronic exposure to polluted air can cause chronic neuroinflammation and death of nerve cells.

It is estimated that up to 65% of risk factors in AD development involve nongenetic factors, as discussed above.

The discovery of a new blood test, called tau blood test (p- tau 217) with results recently published in the medical journal JAMA and presented at the Alzheimer’s Association International Conference, is considered a giant step forward, not only for the early diagnosis (before dementia symptoms) of AD with 98% of accuracy but also the differentiation of AD from other dementia producing brain disorders. It is an immunoassay test, soon to be commercially available for general use.

An effective and safe medication is urgently needed for AD. It appears that big pharma is lobbying hard, and pushing FDA for approval of a new drug called “Aducanumab” which is a monoclonal antibody designed to remove fragments of beta-amyloid from the brain of patients with AD. Yet, clinical trials have shown that none of these types of drugs are effective - even though they remove beta amyloid fragments from the brain, the cognitive decline of patients continuous. Additionally, this new medication has only been tried in mild AD cases, and has caused significant and serious side effects, like brain swelling and brain hemorrhage, which were observed in 40 percent of patients on clinical trials. Furthermore, the drug must be given by monthly IV injections, and the drug alone costs $56,000 a year, and there would be additional, tens of thousands of dollars of hospital, brain imaging (MRI) studies, and follow up medical care costs. The FDA advisory committee should have had serious concerns with the evidence and should not, for whatever reasons, have prematurely approved this drug. When men and women of science approve a drug for non-medical reasons, it is much more disturbing. No wonder, after the approval of the drug by FDA, three scientists resigned from the advisory committee.  This decision would, for sure, bring financial ruin and bankruptcy to many of the 36 million of AD patients and their families.