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Alzheimer’s Disease
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Alzheimer’s disease (AD) is the most common cause of dementia in the elderly.
It is characterized by a progressive loss of memory, reasoning, judgment, and
orientation, by the presence of large numbers of extracellular senile plaques and
intracellular neuroFbrillary tangles, as well as substantial cell loss in the brain.
Genetic studies in early onset families have identiFed mutations in three genes that
cause AD, while genetic studies in sporadic AD have identiFed the apolipoprotein E4
allele as a risk factor for disease.
In vitro
cell biology and transgenic mouse studies
implicate all of these genes in the biology of A
β
metabolism. A consistent effect
of these genetic factors is an increase in A
β
deposition. ±urthermore, cell biology
studies have identiFed targets for possible treatment of AD. Transgenic models are
now being used to test the validity of these targets and therapeutic approaches to the
treatment of AD.
1
Pathology and Epidemiology of Alzheimer’s
Disease
The German psychiatrist Alois Alzheimer
Frst described the clinical and pathological
features of Alzheimer’s disease (AD) in a
55-year-old female patient; he published
the discovery as a case report in 1907. It
was thought that the ‘‘presenile dementia’’
described by Alzheimer was distinct from
‘‘senile dementia’’ seen in older patients,
but it is now widely accepted that the two
conditions are the same disease, differing
primarily in the age of onset.
Alzheimer’s disease is the most com-
mon cause of dementia in the western
world, and the fourth leading cause of
deaths in the United States. The disease is
conFned mainly to aged individuals and
is progressive. It affects 1% of people
in the developed nations and is likely to
become a major problem in developing
countries as the proportion of elderly per-
sons increases in these populations. The
incidence of AD rises with increasing age:
1 to 5% of people aged 65 years are af-
fected, while 10 to 20% of those over the
age of 80 have AD.
The Frst clinical manifestation is usu-
ally a loss of short-term memory; this
is followed, over the next 6 to 20 years,
by a progressive loss of memory, reason-
ing, judgment, and orientation (dementia).
Death occurs, on average, about 10 years
after the onset of symptoms. Many epi-
demiological surveys have been carried
out to identify risk factors. There is a
clear correlation between AD and a pos-
itive family history in about one-third of
cases; the risk of AD is also elevated in
individuals with Down syndrome. Severe
head trauma with loss of consciousness
increases risk for AD, particularly in those
individuals who also have an apolipopro-
tein E4 allele. In contrast, the use of
nonsteroidal anti-inflammatory agents or
cholesterol-lowering agents, such as the
statins, may reduce risk for AD. Another
factor that may potentially decrease risk
for AD is the years of education; the more
the years of education, the lower the risk
of disease.
Alzheimer’s
disease
is
characterized
neuropathologically by the presence of
large numbers of neuritic plaques and neu-
roFbrillary tangles (N±T) within the brain
cortex (±ig. 1). In addition, there is massive
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