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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
"muscle cells"
symptom
cadasil
congenital toxoplasmosis
hereditary cerebral hemorrhage with amyloidosis
inclusion body myositis
kindler syndrome
lymphangioleiomyomatosis
megacystis-microcolon-intestinal hypoperistalsis syndrome
zellweger syndrome
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