Alzheimer's Disease (cont.)
What are causes of Alzheimer's disease?
The cause(s) of Alzheimer's disease is (are) not known. The "amyloid cascade hypothesis" is
the most widely discussed and researched hypothesis about the cause of
Alzheimer's disease. The
strongest data supporting the amyloid cascade hypothesis comes from the study of
early-onset inherited (genetic) Alzheimer's disease. Mutations associated with
Alzheimer's disease have been found
in about half of the patients with early-onset disease. In all of these
patients, the mutation leads to excess production in the brain of a specific
form of a small protein fragment called ABeta (Aβ).
Many scientists believe that in the majority of sporadic (for example, non-inherited)
cases of Alzheimer's disease (these make up the vast majority of all cases of
Alzheimer's disease) there is too
little removal of this Aβ protein rather than too much production. In any case,
much of the research in finding ways to prevent or slow down Alzheimer's disease has focused on
ways to decrease the amount of Aβ in the brain.
What are risk factors for Alzheimer's disease?
The biggest risk factor for Alzheimer's disease is increased age. The likelihood of developing
Alzheimer's disease doubles every 5.5 years from 65 to 85 years of age. Whereas only 1%-2% of
individuals 70 years of age
have Alzheimer's disease, in some studies around 40% of individuals 85 years of
age have
Alzheimer's disease. Nonetheless, at
least half of people who live past the 95 years of age do not have Alzheimer's
disease.
Common forms of certain genes increase the risk of developing Alzheimer's
disease, but do not
invariably cause Alzheimer's disease. The best-studied "risk" gene is the one that encodes
apolipoprotein E (apoE). The apoE gene has three different forms (alleles) --
apoE2, apoE3, and apoE4. The apoE4 form of the gene has been associated with
increased risk of Alzheimer's disease in most (but not all) populations studied. The frequency of
the apoE4 version of the gene in the general population varies, but is always
less than 30% and frequently 8%-15%. Persons with one copy of the E4 gene usually
have about a two to three fold increased risk of developing Alzheimer's disease. Persons with
two copies of
the E4 gene (usually around 1% of the population) have about a nine-fold
increase in risk. Nonetheless, even persons with two copies of the E4 gene don't
always get Alzheimer's disease. At least one copy of the E4 gene is found in 40% of patients with
sporadic or late-onset Alzheimer's disease.
This means that in majority of patients with
Alzheimer's disease, no
genetic risk factor has yet been found. Most experts do not recommend that adult
children of patients with Alzheimer's disease should have genetic testing for the apoE4 gene
since there is no treatment for Alzheimer's disease. When medical treatments that prevent or
decrease the risk of developing Alzheimer's disease become available, genetic testing may be
recommended for adult children of patients with Alzheimer's disease so that they may be treated.
Many, but not all, studies have found that women have a higher risk for
Alzheimer's disease
than men. It is certainly true that women live longer than men, but age alone
does not seem to explain the increased frequency in women. The apparent
increased frequency of Alzheimer's disease in women has led to considerable research about the
role of estrogen in Alzheimer's disease. Recent studies suggest that estrogen should not be
prescribed to post-menopausal women for the purpose of decreasing the risk of
Alzheimer's disease. Nonetheless, the role of estrogen in Alzheimer's disease remains an area of research focus.
Some studies have found that Alzheimer's disease occurs more often among people who suffered
significant traumatic head injuries earlier in life, particularly among those
with the apoE 4 gene.
In addition, many, but not all studies, have demonstrated that persons with
limited formal education - usually less than eight years - are at increased risk for
Alzheimer's disease. It is not known whether this reflects a decreased "cognitive reserve" or
other factors associated with a lower educational level.
Next: How is the diagnosis of Alzheimer's disease made? »
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