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Extracellular matrix modulator lysyl oxidase colocalizes with amyloid-beta pathology in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis--Dutch type.
[hereditary cerebral hemorrhage with amyloidosis]
Accumulation
of
amyloid-
beta
(
Aβ
)
in
brain
vessel
walls
and
parenchyma
,
known
as
cerebral
amyloid
angiopathy
(
CAA
)
and
senile
plaques
(
SPs
)
,
respectively
,
plays
a
key
role
in
Alzheimer
's
disease
(
AD
)
and
hereditary
cerebral
hemorrhage
with
amyloidosis
of
the
Dutch
type
(
HCHWA-D
)
pathogenesis
.
Although
the
mechanisms
underlying
CAA
and
SP
formation
remain
largely
unknown
,
evidence
is
mounting
that
local
alterations
of
the
extracellular
matrix
(
ECM
)
in
the
brain
vessel
wall
and
/
or
parenchyma
play
an
important
role
.
Lysyl
oxidase
(
LOX
,
E
.
C
.
1
.
4
.
3
.
13
)
is
an
inducible
amine
oxidase
that
modulates
the
ECM
by
catalyzing
the
formation
of
molecular
covalent
cross-links
in
ECM
proteins
.
The
aim
of
this
study
is
to
investigate
the
association
of
LOX
with
CAA
and
with
classic
and
diffuse
SPs
in
both
AD
and
HCHWA-D
cases
.
We
observed
an
association
of
LOX
with
Aβ
in
CAA
and
with
Aβ
in
both
classic
and
diffuse
SPs
in
AD
and
HCHWA-D
cases
.
In
addition
,
LOX
staining
was
observed
in
reactive
astrocytes
associated
with
these
lesions
.
We
conclude
that
the
ECM
modulating
enzyme
LOX
is
associated
with
the
Aβ-related
pathological
hallmarks
of
both
AD
and
HCHWA-D
,
and
that
our
findings
provide
additional
insights
into
the
mechanisms
underlying
the
formation
of
these
lesions
.
Diseases
Validation
Diseases presenting
"brain vessel walls"
symptom
hereditary cerebral hemorrhage with amyloidosis
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