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Epigenetics and Alzheimer’s disease

Epigenetics is hot! Epigenetics is the study of the changes in the expression of organisms caused by the modification of genetic expression rather than alteration of DNA itself. Epigenetics can be used to optimize wellness potential or in the custom prevention and the custom treatment of disease. No better example for epigenetics and disease exists than the relationship between epigenetics and Alzheimer’s disease.

What Is Alzheimer’s Disease?

Alzheimer’s disease is an irreversible type of dementia, according to the Centers for Disease Control and Prevention (CDC.) It is a progressive brain disease that affects approximately 5.4 million Americans. It ranks sixth among adults as the leading cause of death and is the fifth leading cause of death for Americans aged 65 and older.  Forty-four million are effected worldwide, with 5.5 million effected in the U.S.  The incidence of Alzheimer’s disease is higher in women with current numbers at 3.3 million.  The number of individuals diagnosed with Alzheimer’s disease doubles every 5 years in those > 65.  Alzheimer’s disease is not confined to those > 65 and older, early onset Alzheimer’s disease effects adults < 65 and younger and early Alzheimer’s disease accounts for 5% of total cases.

Alzheimer’s robs its victims of their memories, their identities, their personalities and eventually their lives.  Alzheimer’s disease develops slowly over time and is never a normal part of aging. It is an insidious disease that takes its toll on individuals and their families.


Trends in Alzheimer’s Management

According to the CDC, the number of older adults diagnosed with Alzheimer’s is “unprecedented.” In 2015, a full 15 percent of America’s population was age 65 or older, the most likely age group effected by Alzheimer’s disease. Predictions put the number of Americans in this age group at 98 million by 2060.  Current estimates are that the number of individuals diagnosed with Alzheimer’s disease will reach 16 million in the U.S. by 2050.

Total payments in 2017 for Alzheimer’s-related health care, long-term care and hospice reached an estimated $259 billion. Medicare covered only about half of these costs. There are an estimated 15 million Americans in 2017 providing more than 18.2 billion hours of care to family members and friends with Alzheimer’s and other dementias. These caregivers are unpaid for their efforts, a total value estimated at over $230 billion.  By 2050, the projected annual total costs of Alzheimer’s disease and other dementias in Americans > 65 only, excluding those < 65,  is expected to exceed 1 trillion dollars.  You read that right, 1 trillion with a ’T’.



The exact cause of this disease is not yet fully understood. According to the Mayo Clinic, Alzheimer’s disease results from a combination of lifestyle, environmental and genetic factors.

In Alzheimer’s, the affected brain has far fewer functioning cells and far fewer connections between cells than a healthy brain. Cell death leads to significant shrinkage of the brain. The 4 abnormalities that are hallmarks of the disease include:

  • Plaques. These are masses of beta-amyloid proteins that hamper and destroy cell-to-cell communication by collecting on the outside of brain cells, causing damage to the connections between the brain cells, called synapsis, leading to tau protein tangles and cognitive decline.  This Amyloid-beta cascade hypothesis (known as the ABC hypothesis) has been the historical, primary focus of research and the primary hypothesis of Alzheimer’s disease development.
  • Tangles. Tau proteins, a necessary support protein to the cell’s internal support and nutrient transport system, becomes twisted into abnormal tangles inside brain cells. The cell’s transport system fails, depriving the cell of nutrients and other essential materials.
  • Deficits in cholinergic function, which can affect cognition and behavioral traits and interfere with activities of daily living. Acetylcholinesterase (AChE) inhibition is the focus much of pharmacological intervention. Data collection around the effects of cholinergic function deficiency shows levels of AChE and choline acetyl-transferase decrease by as much as 90 percent in severe Alzheimer’s disease.
  • Inflammation.  Whatever the cause of inflammation (i.e. heavy metals, virus, toxins…), inflammation is a pre-requisite for all chronic diseases of Aging and Alzheimer’s disease is no different.  Some of the most potent immune cells in the body, microglia cells, exist in the brain.  Chronic activation of microglia cells in the brain produces massive inflammation that results in major collateral damage that can lead to damage to the areas of the brain that can lead to Alzheimer’s disease.  This process is called excitotoxicity.   The well known Herpes simplex 1 virus (oral herpetic ulcers) is one such example.  The reactivation of latent Herpes simplex 1 virus has been shown to cause uncontrolled inflammation, excitotoxicity, and neurodegeneration.
  • Oxidative stress and Mitochondrial dysfunction.  Mitochondria are the energy power houses of the cell.  High oxidative stress will compromise mitochondrial function and lead to cell dysfunction.  The loss of a cell’s ability to make energy will lead to cell dysfunction, chronic immune dysfunction, and cell death.  If this dysfunction destruction occurs in the brain, neurodegeneration and Alzheimer’s disease can be the result.


Epigenetics and Alzheimer’s Disease

Alzheimer’s disease occurs in two types, early-onset and late-onset, and both have epigenetic components. Epigenetics references modifications to DNA that are external in nature, meaning there is no change in the base DNA sequence of genes, but there is a change in the expression of the genes.  Single Nucleotide Polymorphisms, or SNPs, are the most common cause of variations in genetic expression.  Each individual’s unique genome is the totality of their genetic code found in their deoxyribonucleic acid (DNA). The epigenome is the total collection of the proteins and chemical compounds that attach to DNA that modify its expression and thus change function. These modifications don’t alter the DNA sequence, instead, they alter the utilization of the DNA’s instructions within the cell.  For more in-depth discussion, see my previous post—Your DNA is not your Destiny.

There are numerous SNPs implicated in Alzheimer’s disease.  The apolipoprotein E (APOE) gene on chromosome 19 is one of the most implicated SNPs in Alzheimer’s disease risk.  The APOE4 gene has been shown to increase viral potency, infectivity rates, and reactivation thus increasing Alzheimer’s disease risk based on the viral/inflammatory interaction described above. The APOE SNP rs429358 is associated with a 12 fold increase for late-onset Alzheimer’s disease and a 61 fold increase for early-onset disease.  The rs4420638 SNP, another APOE SNP, is associated with a 25 fold increase beyond that of the rs429358.  Additional APOE SNPs that increase Alzheimer’s disease risk include the SNP, rs7412, which increases the risk of late-onset disease and the PLD3 gene SNP, rs145999145, that doubles the overall risk of disease.  The TREM2 genetic SNP rs75932628 shows a strong, highly significant association with Alzheimer’s disease.  Not all genetic SNPs increase Alzheimer’s disease risk.  The APP gene SNP rs63750847 is associated with a 3.5 fold reduction and a 4 fold resistance to Alzheimer’s disease.


Treatment Options with epigenetics

The key to the treatment of Alzheimer’s disease is prevention.  A lifestyle that includes a highly nutritional diet, physical activity, active social engagement and mental stimulation can improve the quality of life as people age. A lifestyle fashioned around these basic guidelines can help reduce the risk of cognitive decline and associated diseases such as Alzheimer’s.   A recent report from the Lancet Commission on Dementia Prevention and Care points to Lifestyle changes as key in the prevention of dementia risk.

The use of epigenetics in Alzheimer’s disease is an assessment of probability.   This probability risk assessment allows action to be taken prior to even the smallest dysfunction and long before major dysfunction and damage occur.  Even early disease diagnosis is too late.

Epigenetics integrates the evidence into customized medicine.  Coconut oil is a perfect example of how epigenetics helps to integrate customized therapy.  Coconut oil, a saturated fat, is advocated by research and by many for the prevention and treatment of Alzheimer’s disease.  I don’t disagree that coconut oil is beneficial for some individuals.  However, Single Nucleotide Polymorphisms in the PPARG and TNF genes are associated with significantly increased inflammation with saturated fat intake.  Customization is the key to risk assessment: in the case of SNPs with the PPARG and TNF genes, coconut oil will actually increase inflammation, increase Alzheimer’s disease risk, and thus is contraindicated for these individuals.  This example is the customization potential provided by epigenetics to individualize therapy.

To learn how to customize your wellness lifestyle and customize your prevention or treatment strategy for Alzheimer’s disease, call our office at 865.675.9355 today.

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