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Heparan sulfate proteoglycan expression in cerebrovascular amyloid beta deposits in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis (Dutch) brains.
[hereditary cerebral hemorrhage with amyloidosis]
Cerebrovascular
deposition
of
amyloid
beta
protein
(
A
beta
)
is
a
characteristic
lesion
of
Alzheimer
's
disease
(
AD
)
and
hereditary
cerebral
hemorrhage
with
amyloidosis
of
the
Dutch
type
(
HCHWA-D
)
.
Besides
A
beta
,
several
other
proteins
and
proteoglycans
accumulate
in
cerebral
amyloid
angiopathy
(
CAA
)
.
We
have
now
analyzed
the
expression
of
the
heparan
sulfate
proteoglycan
(
HSPG
)
subtypes
agrin
,
perlecan
,
glypican-
1
,
syndecans
1
-
3
and
HS
glycosaminoglycan
(
GAG
)
side
chains
in
CAA
in
brains
of
patients
with
AD
and
HCHWA-D
.
Hereto
,
specific
well-characterized
antibodies
directed
against
the
core
protein
of
these
HSPGs
and
against
the
GAG
side
chains
were
used
for
immunostaining
.
Glypican-
1
was
abundantly
expressed
in
CAA
both
in
AD
and
HCHWA-D
brains
,
whereas
perlecan
and
syndecans-
1
and
-
3
were
absent
in
both
.
Colocalization
of
agrin
with
vascular
A
beta
was
clearly
observed
in
CAA
in
HCHWA-D
brains
,
but
only
in
a
minority
of
the
AD
cases
.
Conversely
,
syndecan-
2
was
frequently
associated
with
vascular
A
beta
in
AD
,
but
did
not
colocalize
with
vascular
A
beta
deposits
in
HCHWA-D
.
The
three
different
syndecans
,
agrin
,
glypican-
1
and
HS
GAG
,
but
not
perlecan
,
were
associated
with
the
majority
of
senile
plaques
(
SPs
)
in
all
brains
.
Our
results
suggest
a
role
for
agrin
in
the
formation
of
SPs
and
of
CAA
in
HCHWA-D
,
but
not
in
the
pathogenesis
of
CAA
in
AD
.
Both
syndecan-
2
and
glypican
,
but
not
perlecan
,
may
be
involved
in
the
formation
of
CAA
.
We
conclude
that
specific
HSPG
species
may
be
involved
in
the
pathogenesis
of
CAA
in
both
AD
and
HCHWA-D
,
and
that
the
pathogenesis
of
CAA
and
SPs
may
differ
with
regard
to
the
involvement
of
HSPG
species
.
Diseases
Validation
Diseases presenting
"were associated with the majority of senile plaques"
symptom
hereditary cerebral hemorrhage with amyloidosis
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