Alzheimer's Disease Causes
While much progress has
been made in Alzheimer’s disease (AD) research, the exact cause is unknown. Many
scientists believe that a buildup of two abnormal structures in the brain play
an important role. These structures are called amyloid plaques and neurofibrillary tangles.
Amyloid plaques are
dense, mostly insoluble clumps of protein fragments. They leave a highly
damaging substance outside and around the brain’s nerve
People with AD have a buildup
of these plaques in their hippocampus. The hippocampus is involved with memory,
including how immediate or short-term memories are stored into long-term
Your ability to function
in everyday life also can be affect by an unhealthy hippocampus. Everything you
do involves your ability to acquire, store, and retrieve memories. This can be
anything from remembering if you ate lunch, to recognizing a loved one, to
recalling if you turned off the stove.
The hippocampus also is
essential to both spatial memory and spatial navigation. Spatial memory is how
you retain information about your surroundings. Spatial navigation involves how
you travel to a destination. Research suggests early hippocampus damage may
explain why AD sufferers often wander and get lost.
are insoluble, twisted fibers that clog the brain from the inside-out.
Brain nerve cells
(called neurons) have a special transport system called microtubules. It acts
like railroad tracks, and safely guides and transports nutrients, molecules,
and information to other cells. An important fiber-like protein called tau is responsible for keeping
those microtubules stable.
The tau’s chemical
make-up is altered in people with AD. The threads of tau become tangled and
twisted. Thus, the microtubules become unstable and disintegrate, which
collapses the entire neuron transport system.
This series of events
may be related to the first visible sign of AD: memory loss. More research is
needed to determine if amyloid plaques, tangles, and tau are a direct
cause of AD.
Genetics of Alzheimer’s Disease
Researchers are certain
of a genetic component to AD. In the elderly, the gene most associated with the
onset of symptoms is located on chromosome 19. It’s called apolipoprotein
There are several
versions (alleles) of APOE. According to the National
Institute on Aging, about 40 percent of people who develop AD later in life
have an APOE e4 allele. A blood test can determine if you have it.
But it’s still not
possible to predict who will develop AD. Some people with one or even two APOE
e4 alleles never develop the disease. Others who get AD don’t have any APOE e4
alleles. Still, an “AD gene” does increase your risk.
One of these newly
identified genes that increase your risk is CD33. It causes the body to not
eliminate as many amyloid plaques as it should. And scientists have long
believed amyloid plaques — and more specifically their building up to toxic
levels — likely plays a key role in degradation of brain neurons.
Genetics of Early-Onset AD
Genetic studies of
families with a history of early-onset AD have identified mutations
in three different genes.
- APP (on chromosome 21)
- PSEN-1 (on chromosome 14)
- PSEN-2 (on chromosome 1)
These genes are thought
to be responsible for the rare form of AD that afflicts men and women in their
early 30s or 40s. They are believed to help produce amyloid protein, which
forms amyloid plaques and are the hallmarks of AD. These mutated genes do not
play a role in the more common late-onset AD.
Approximately 50 percent of people who
have a parent with early-onset AD will likely inherit the genetic mutation and
develop the disease. For those young individuals where neither parent had
early-onset AD, research has found that often a second-degree relative (e.g.,
an uncle, aunt, and/or grandparent) suffered from the condition.