Rare Diseases Symptoms Automatic Extraction
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Abeta is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis.
[hereditary cerebral hemorrhage with amyloidosis]
The
E
693
Q
mutation
in
the
amyloid
beta
precursor
protein
(
APP
)
leads
to
cerebral
amyloid
angiopathy
(
CAA
)
,
with
recurrent
cerebral
hemorrhagic
strokes
and
dementia
.
In
contrast
to
Alzheimer
disease
(
AD
)
,
the
brains
of
those
affected
by
hereditary
cerebral
hemorrhage
with
amyloidosis
-
Dutch
type
(
HCHWA-D
)
show
few
parenchymal
amyloid
plaques
.
We
found
that
neuronal
overexpression
of
human
E
693
Q
APP
in
mice
(
APPDutch
mice
)
caused
extensive
CAA
,
smooth
muscle
cell
degeneration
,
hemorrhages
and
neuroinflammation
.
In
contrast
,
overexpression
of
human
wild-
type
APP
(
APPwt
mice
)
resulted
in
predominantly
parenchymal
amyloidosis
,
similar
to
that
seen
in
AD
.
In
APPDutch
mice
and
HCHWA-D
human
brain
,
the
ratio
of
the
amyloid-
beta
40
peptide
(
Abeta
40
)
to
Abeta
42
was
significantly
higher
than
that
seen
in
APPwt
mice
or
AD
human
brain
.
Genetically
shifting
the
ratio
of
AbetaDutch
40
/
AbetaDutch
42
toward
AbetaDutch
42
by
crossing
APPDutch
mice
with
transgenic
mice
producing
mutated
presenilin-
1
redistributed
the
amyloid
pathology
from
the
vasculature
to
the
parenchyma
.
The
understanding
that
different
Abeta
species
can
drive
amyloid
pathology
in
different
cerebral
compartments
has
implications
for
current
anti-amyloid
therapeutic
strategies
.
This
HCHWA-D
mouse
model
is
the
first
to
develop
robust
CAA
in
the
absence
of
parenchymal
amyloid
,
highlighting
the
key
role
of
neuronally
produced
Abeta
to
vascular
amyloid
pathology
and
emphasizing
the
differing
roles
of
Abeta
40
and
Abeta
42
in
vascular
and
parenchymal
amyloid
pathology
.
Diseases
Validation
Diseases presenting
"amyloidosis"
symptom
cadasil
fabry disease
familial mediterranean fever
hereditary cerebral hemorrhage with amyloidosis
lymphangioleiomyomatosis
phenylketonuria
systemic capillary leak syndrome
triple a syndrome
waldenström macroglobulinemia
This symptom has already been validated