Alzheimer’s Disease
183
Fig. 1
Plaques and tangles in an AD brain. Shown is a brain section from an
individual with mild AD. The section was double-stained with antibody PHF-1
speci±c to tangles and 10D5 speci±c to
β
-amyloid. Courtesy of Dr. Joel Price.
neuronal cell loss, and amyloid deposits
that occur in the walls of the blood ves-
sels of the meninges and cerebral cortex.
NeitherplaquesnortanglesarespeciFcto
AD – they occur in intellectually normal,
elderly people and in certain other dis-
eases. However, they are more numerous
and more widely distributed throughout
the brains of Alzheimer’s patients. Senile
plaques are extracellular deposits, while
tangles initially appear within the degen-
erating neurons. The major proteinaceous
constituent of plaques is a 39 to 43 amino
acid peptide called
β
-amyloid, or A
β
.The
microtubule-associated protein, tau, is a
major constituent of tangles. In the AD
brain, there is extensive activation of as-
trocytes and microglia, the two primary
mediators of inflammation in the central
nervous system (CNS). A large number
of inflammatory mediators and comple-
ment components are elevated in the AD
brain, and colocalized with both plaques
and tangles. The inflammatory response
might be induced by increased A
β
levels
or by plaque formation.
The deposition of A
β
has also been ob-
served in association with several other
pathological conditions. Individuals with
Down
syndrome,
who
live
into
their
late thirties and beyond, develop a neu-
ropathology indistinguishable from that of
AD. Temporal studies in Down syndrome
suggest that A
β
deposition is the earli-
est of the known pathological markers
to appear, and that neuroFbrillary tan-
gles and neuronal cell loss occur decades
after the Frst A
β
deposition. However,
dementia correlates more closely with neu-
roFbrillary tangles and neuron loss than
with plaques. According to one hypothe-
sis based on these observations, amyloid
deposition precedes and induces tangle
formation; tangles (and perhaps plaques)
cause
neuronal
death,
and
the
resul-
tant neuronal damage destroys important
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