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Increased cystatin C in astrocytes of transgenic mice expressing the K670N-M671L mutation of the amyloid precursor protein and deposition in brain amyloid plaques.
[hereditary cerebral hemorrhage with amyloidosis]
Cystatin
C
is
an
essential
secretory
cofactor
for
neurogenesis
with
potent
protease
inhibitor
activities
.
Polymorphisms
of
cystatin
C
are
genetically
associated
with
Alzheimer
's
disease
(
AD
)
,
and
the
L
68
Q
mutation
causes
hereditary
cerebral
hemorrhage
with
amyloidosis
of
the
Icelandic
type
,
in
which
cystatin
C
and
beta
-amyloid
are
colocalized
in
cortical
blood
vessels
.
To
determine
whether
cystatin
C
and
beta
-amyloid
also
colocalize
in
brain
amyloid
plaques
,
we
analyzed
transgenic
mice
expressing
the
Swedish
APP
(
SweAPP
)
mutation
.
We
found
high
levels
of
cystatin
C
in
astrocytes
surrounding
beta
-amyloid
plaques
,
and
discrete
layers
of
cystatin
C
attached
to
amyloid
plaque
cores
covered
by
a
layer
of
beta
-amyloid
.
In
addition
,
cystatin
C
accumulated
in
reactive
astrocytes
throughout
the
brain
,
independently
of
,
and
before
the
onset
of
,
amyloid
plaque
formation
.
These
results
show
that
expression
of
SweAPP
is
associated
with
increased
cystatin
C
in
reactive
astrocytes
,
and
they
suggest
an
early
role
of
cystatin
C
in
appositional
amyloid
plaque
growth
.
Diseases
Validation
Diseases presenting
"we analyzed transgenic mice expressing the swedish app"
symptom
hereditary cerebral hemorrhage with amyloidosis
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