Dr. Alois Alzheimer was a German psychiatrist and neuropathologist. He first identified presenile dementia in 1906.

First identified by Dr. Alois Alzheimer in 1906, Alzheimer’s is the most common type of dementia.

Physically, the brains of Alzheimer’s patients show characteristic shrinkage and damage in certain regions of the brain, particularly those that subserve memory.  Alzheimer’s is a progressive disease that eventually leads to the loss of brain function in key areas, including those critical for speaking, recognizing people, calculating, focusing, and performing basic tasks.  Dr. Alzheimer found that individuals suffering from the disease have large buildups of amyloid plaques in their brain (although early on, some people with these clumps do not exhibit symptoms of Alzheimer’s).

Alzheimer’s manifests itself by increasing cognitive decline, including the loss of short-term memory, difficulty with languages, disorientation, mood swings, emotional disorders such as depression, the loss of ability to complete complex actions (like getting dressed), feeling lost or easily confused, and withdrawing from social relationships, including friends and family.

Today, Alzheimer’s is the third leading cause of death[1] in the United States.  Many of the same issues that increase risk for Alzheimer’s are also connected to cardiovascular disease and autoimmune disorders, meaning that treatments to prevent Alzheimer’s may help protect against two other common causes of death.

Alzheimer’s is primarily a disease that strikes older adults, although symptoms may begin even in the 40s or 50s.  Today, approximately 5.4 million Americans are living with the disease, although statistics suggest that as many as 45 million of the currently living Americans may develop Alzheimer’s disease.  The majority of Alzheimer’s cases are classified as “late onset” Alzheimer’s, with the first symptoms becoming apparent after age 65.  There is also a less common form of the disease called “early onset” Alzheimer’s that primarily affects people in their 40s and 50s.  Today, approximately 200,000 people[2] have the early onset form of Alzheimer’s.

Since it was first identified more than 100 years ago, scientists have been working to understand what causes Alzheimer’s.  Exposure to toxins (including mercury and aluminum), hormonal imbalances, nutritional deficiencies, and genetic factors have all been explored, but it was the identification of the APOE-4 gene variant that has shown the most promise because individuals with one or more copies of APOE-4 have been shown to have a far higher risk of developing Alzheimer’s.

The research performed by Dr. Bredesen and his colleagues is extremely significant because it has identified the pathways by which Alzheimer’s develops, as well as revealing subtypes of Alzheimer’s for the first time.

The brain is a complex organ and relies on a carefully balanced system of chemical markers to regulate brain health.  Everyone has the APOE gene on chromosome 19, but it is the APOE-4 variant (called an allele) that plays a key role in sending harmful messages that result in amyloid-beta plaque buildup and the destruction of brain cells that lead to the symptoms of Alzheimer’s, especially those that handle memory.

The APOE gene regulates many different bodily functions, both inside and outside of the brain.  When the body is under attack (inflammation) or senses a deficiency such as vitamin D (or any of many others) or senses toxins, it then signals the amyloid precursor protein (APP) located in the brain to take action.

The easiest way to think of an APP molecule—which is what produces the amyloid—is to think of it being a CEO of a company, responding to the status of many different things such as controversy (inflammation), stock price (nutritional support), and sabotage (toxin exposure).

In a healthy person, the APP molecule is cut mostly into two different parts, launching two good fragments that then activate cells locally to strengthen and protect the memories and synapses, including the production of chemical messengers known as neurotransmitters.  Neurotransmitters are molecules that coordinate communication across the brain, and are vital for tasks like storing, recalling, and forming memories.

But when the body is suffering from nutritional deficiencies or is under attack from inflammation or toxins (especially if you have the APOE-4 variant), there are different instructions for the APP molecules.  Instead of dividing into two healthy fragments, the APP then launches four signals that activate the pull-back of brain cell connections, memory loss, and ultimately destruction of the brain cells.

The process by which APP molecules are told which signals to launch is called proteolysis, and this involves cutting the APP with molecular scissors called proteases.  Specific enzymes divide or cut the molecule into different segments.  These segments make all the difference, the same way a few lines of code in a program can hack a person’s computer.

When proteases cut the APP molecules at three specific locations, this produces four chemical messengers known as peptides.  The four dangerous peptides are known as soluble APP beta, Jcasp, C31, and amyloid-beta (this last one is what forms the amyloid in the brains of patients with Alzheimer’s disease).  Once launched, each plays a specific role in triggering cell destruction.

Launching these harmful signals does not immediately lead to Alzheimer’s or other related diseases like cardiovascular illness and autoimmune disorders, but begins a downward path that takes years.  Instead, these signals are responding to a body that is out of balance.  In the early stages, only some APP molecules may be launching harmful signals while the majority continue to function normally (launching the “good” signals).  Alzheimer’s is a progressive disease, meaning that it gets worse over time.  Conversely, because Alzheimer’s is caused by imbalances, proactive steps can help tilt the balance the other way, leading to the reversal of damage.

Each of the four harmful peptides plays a specific role in causing destruction in the cells.  For instance, the peptide amyloid-beta affects other APP molecules in the brain, causing them to release even more amyloid-beta (a kind of snowball effect), believed to be the cause of the buildup of amyloid-beta plaques in the brains of people with Alzheimer’s.

The key to preventing and even reversing the effects of Alzheimer’s is to understand the vital role that the APOE gene, and other factors, play in regulating APP molecules.  When the body senses inflammation or nutritional deficiencies or toxin exposure, the APOE protein then triggers the APP to launch specific signals to handle the problem.  In short, if there is no cause for alarm, the APOE gene will not tell the APP molecules in the brain to launch the negative signals.

Individuals with the APOE-4 variant are, effectively, more sensitive to overreaction to alarm, thus responding more vigorously with instructions to the APP molecules to launch the four harmful signals.  Therefore, individuals with one or more copies of the APOE-4 gene are at a higher risk for developing Alzheimer’s.  Again, regardless of risk factors, not everyone with the APOE-4 gene does develop Alzheimer’s, and not everyone who lacks the APOE-4 allele are certain to avoid it.

Once the nutritional deficiencies and causes for inflammation and toxic exposures in cell tissue are reduced or eliminated, the APP molecules will not respond in a destructive manner.  Instead, the positive signals will be launched that protect and promote healthy cell development, including key areas of the brain that handle memory.  Under normal circumstances, the good signals launched by the APP molecules combat the progression of Alzheimer’s.

[1] https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet

[2] http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers/art-20048356