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Age-related plaque morphology and C-terminal heterogeneity of amyloid beta in Dutch-type hereditary cerebral hemorrhage with amyloidosis.
[hereditary cerebral hemorrhage with amyloidosis]
The
evolvement
of
amyloid
beta
(
Abeta
)
deposition
in
the
frontal
cerebral
cortex
of
24
patients
of
increasing
age
with
Dutch
-
type
hereditary
cerebral
hemorrhage
with
amyloidosis
(
HCHWA-D
)
was
studied
using
end-
specific
monoclonal
antibodies
to
Abetax-
42
(
Abeta
42
)
or
Abetax-
40
(
Abeta
40
)
and
markers
for
degenerating
neurites
.
Abeta
42
immunostaining
revealed
parenchymal
Abeta
deposits
with
a
heterogeneous
morphology
and
distribution
,
i
.
e
.
,
clouds
,
fine
/
dense
diffuse
,
coarse
,
and
homogeneous
plaques
.
Clouds
and
diffuse
plaques
were
associated
with
glial
Abeta
granules
.
Abeta
40
labeling
was
absent
in
clouds
/
fine
diffuse
plaques
,
inconsistent
and
variably
intense
in
dense
diffuse
/
coarse
plaques
and
consistent
in
homogeneous
plaques
.
In
a
subset
of
Abeta
40
-
positive
plaques
,
degenerating
neurites--without
tauopathy--and
/
or
amyloid
cores
were
observed
.
Electron
microscopy
revealed
no
apparent
amyloid
fibrils
in
fine
diffuse
plaques
,
small
bundles
of
fibrils
in
dense
diffuse
/
homogeneous
plaques
,
and
amyloid
masses
in
coarse
plaques
.
The
parenchymal
Abeta
pathology
was
age-related
:
the
ratio
of
fine
to
dense
diffuse
plaques
decreased
with
age
,
clouds
were
limited
to
younger
patients
;
coarse
plaques
to
the
oldest
old
.
Homogeneous
/
cored
plaques
were
present
most
consistently
in
older
patients
.
Plaque
density
did
not
increase
with
age
.
Vascular
Abeta
deposits
stained
for
both
Abeta
species
,
but
exclusively
Abeta
42
-
positive
,
presumably
recent
deposits
were
also
observed
.
This
study
suggests
that
HCHWA-D
is
a
model
of
plaque
evolution
in
which
clouds
leave
fine
diffuse
plaques
,
which
may
become
dense
diffuse
and
ultimately
coarse
or
homogeneous
plaques
.
Diseases
Validation
Diseases presenting
"dense diffuse"
symptom
hereditary cerebral hemorrhage with amyloidosis
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