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Toxicity of various amyloid beta peptide species in cultured human blood-brain barrier endothelial cells: increased toxicity of dutch-type mutant.
[hereditary cerebral hemorrhage with amyloidosis]
The
amyloid
beta
peptide
(
A
beta
)
is
the
major
component
of
the
neuritic
and
cerebrovascular
amyloid
plaques
that
are
one
of
the
characteristic
features
of
Alzheimer
's
disease
(
AD
)
.
This
peptide
has
been
shown
to
be
toxic
to
several
relevant
cell
types
,
including
neurons
,
cerebrovascular
smooth
muscle
cells
,
and
endothelial
cells
.
We
have
studied
the
toxic
effects
of
both
soluble
and
aggregated
species
of
A
beta
(
1
-
40
)
and
the
mutation
A
beta
(
1
-
40
)
Glu--
>
Gln
(
22
)
,
which
is
the
major
species
deposited
in
the
cerebrovascular
blood
vessels
of
victims
of
hereditary
cerebral
hemorrhage
with
amyloidosis
,
Dutch
type
.
We
find
that
aggregates
of
both
peptides
,
as
well
as
of
A
beta
(
1
-
42
)
and
A
beta
(
25
-
35
)
,
are
toxic
to
cultured
human
cerebrovascular
endothelial
cells
(
hBEC
)
obtained
from
the
brain
of
a
victim
of
AD
(
at
doses
lower
than
those
that
are
toxic
to
CNS
neurons
or
leptomeningeal
smooth
muscle
cells
)
.
Soluble
A
beta
(
1
-
40
)
Gln
(
22
)
is
equally
toxic
to
hBEC
,
whereas
wild-
type
A
beta
(
1
-
40
)
is
toxic
only
at
higher
doses
.
This
toxicity
is
seen
at
the
lowest
dose
of
A
beta
(
1
-
40
)
Gln
(
22
)
used
,
20
nM
.
The
soluble
A
beta
(
1
-
40
)
Gln
(
22
)
aggregates
on
the
surface
of
the
cells
,
in
contrast
to
A
beta
(
1
-
40
)
,
and
its
toxicity
can
be
blocked
both
by
an
inhibitor
of
free
radical
formation
and
by
Congo
red
,
which
inhibits
amyloid
fibril
formation
.
We
discuss
the
possibility
that
the
enhanced
toxicity
of
A
beta
(
1
-
40
)
Gln
(
22
)
is
mediated
by
a
A
beta
receptor
on
the
endothelial
cells
.
Diseases
Validation
Diseases presenting
"blood vessels"
symptom
cadasil
coats disease
cushing syndrome
esophageal adenocarcinoma
hereditary cerebral hemorrhage with amyloidosis
hydrocephalus with stenosis of the aqueduct of sylvius
liposarcoma
lymphangioleiomyomatosis
malignant atrophic papulosis
oral submucous fibrosis
pyomyositis
sneddon syndrome
von hippel-lindau disease
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