In a previous post (apoE4and Genetic Mediated Risk of Alzheimer’s blog) we talked about apoE and the various forms such as
apoE3 and apoE4 that are genetically determined. ApoE is an apo protein that does several
tasks such as carry cholesterol around the body. The important task regarding Alzheimer’s
Disease risk is that it is also used to remove beta amyloid (β amyloid),
the abnormal protein that causes the brain degeneration in Alzheimer’s, from
the brain. The apoE4 variant does not
work well in this capacity to remove this toxic protein from the brain.
An important
concept is that the brain is always making some beta amyloid. The amount it makes is dependent on the brain’s
“environment”. When the brain has low
energy, is under toxic stress or has some other “environmental challenge,” it
produces more beta amyloid which causes neurons to lose connections with other
cells and eventually to kill some brain cells also. This is referred to as “programed downsizing”
during times of some sort of stressor.
When the brain’s environment improves, the β amyloid
is removed and the brain begins to establish more connections, “programed
learning”.
A single
neuron can establish up to about 200 connections with other neurons when in a
healthy environment. This complexity of
how the human brain is “wired” is understood appreciating that there are 80
billion neurons with up to 200 connections each. This collection of 80 billion x 200 potential
connections allows all of the complex tasks the brain does including the
formation and maintenance of memories.
When the
brain environment is “stressed”, β amyloid (yellow structures) is
produced causing this programed downsizing by removing dendrites and thus
connections to other
cells which results in loss of some functions.
Eventually
with continued β amyloid build-up neurons themselves
will become injured and die. At this
point, significant progression in the disease occurs.
The identified
factors that create the “stressed brain environment” include factors such as
chronic inflammation, insulin resistance/diabetes, low hormone levels, chronic
psychosocial stress and many others.
Some of the most important ones are reviewed in a previous post. (Lifestyle Factors and Alzheimer’s/Dementia Risk)
Another
factor in a stressed brain environment is the apoE4 variant. One of the important jobs of apoE is it is 1
of the 3 important mechanisms the brain uses to remove β
amyloid. Basically, the build-up of β amyloid
in the brain is the combined result of the stressors that cause excessive
production and the efficiency of the removal.
ApoE4 is impaired in its ability to remove β amyloid
so it importantly increases disease risk.
The other
two mechanisms of removing β amyloid are through insulin action
and by a white blood cell called a macrophage.
The ability of macrophages to remove β amyloid is dependent on the cell
membrane content of omega-3 fatty acids making careful attention to their
intake important. Insulin
resistance/diabetes hits both sides of the excessive production/removal
balance. It causes excessive β amyloid
production and impairs the ability to remove it efficiently.
The
important take away about apoE is two-fold. The first part is to know what one’s
genetic type is which can be obtained easily by genetic testing. The second part is to optimize lifestyle to
carefully limit β amyloid production given the
impaired ability the apoE4 genotype creates in removing it.
Not everyone
with apoE4 will develop the disease as they may have a protective lifestyle
balance. Many people without the apoE4
variant will still develop the disease as bad lifestyle/environment can overwhelm the balance of β amyloid production/removal. Approximately 1 in 3 adults have either one
or two copies of the apoE4 gene and therefore are at increased risk of
Alzheimer’s.
While we do
not control the genetic cards we are dealt, we do control the lifestyle
environment we put our system in.
