Journal of Clinical Investigation,
Journal Year:
2020,
Volume and Issue:
131(1)
Published: Sept. 29, 2020
Dysfunction
of
immune
and
vascular
systems
has
been
implicated
in
aging
Alzheimer
disease;
however,
their
interrelatedness
remains
poorly
understood.
The
complement
pathway
is
a
well-established
regulator
innate
immunity
the
brain.
Here,
we
report
robust
age-dependent
increases
inflammation,
peripheral
lymphocyte
infiltration,
blood-brain
barrier
(BBB)
permeability.
These
phenotypes
were
subdued
by
global
inactivation
endothelial
cell–specific
ablation
C3ar1.
Using
an
vitro
model
BBB,
identified
intracellular
Ca2+
as
downstream
effector
C3a/C3aR
signaling
functional
mediator
cadherin
junction
integrity.
Endothelial
C3ar1
also
dampened
microglia
reactivity
improved
hippocampal
cortical
volumes
brain,
demonstrating
crosstalk
between
brain
vasculature
dysfunction
cell
activation
neurodegeneration.
Further,
prominent
C3aR-dependent
inflammation
was
observed
tau-transgenic
mouse
model.
Our
studies
suggest
that
heightened
through
cells
promotes
BBB
contributes
to
overall
neuroinflammation
neurodegenerative
disease.
Frontiers in Neuroscience,
Journal Year:
2021,
Volume and Issue:
15
Published: Aug. 19, 2021
The
blood-brain
barrier
(BBB)
plays
a
vital
role
in
maintaining
the
specialized
microenvironment
of
neural
tissue.
It
separates
peripheral
circulatory
system
from
brain
parenchyma
while
facilitating
communication.
Alterations
distinct
physiological
properties
BBB
lead
to
breakdown
associated
with
normal
aging
and
various
neurodegenerative
diseases.
In
this
review,
we
first
briefly
discuss
process,
then
review
phenotypes
mechanisms
that
further
cause
neurodegeneration
cognitive
impairments.
We
also
summarize
dementia
such
as
Alzheimer's
disease
(AD)
vascular
(VaD)
subsequently
disruption
correlated
cognition
decline.
Overlaps
between
AD
VaD
are
discussed.
Techniques
could
identify
biomarkers
summarized.
Finally,
concluded
be
used
an
emerging
biomarker
assist
diagnose
impairment
dementia.
Alzheimer s & Dementia,
Journal Year:
2020,
Volume and Issue:
16(11), P. 1571 - 1581
Published: Aug. 12, 2020
We
have
provided
an
overview
on
the
profound
impact
of
COVID-19
upon
older
people
with
Alzheimer's
disease
and
other
dementias
challenges
encountered
in
our
management
dementia
different
health-care
settings,
including
hospital,
out-patient,
care
homes,
community
during
pandemic.
also
proposed
a
conceptual
framework
practical
suggestions
for
providers
tackling
these
challenges,
which
can
apply
to
general,
or
without
neurological
diseases,
such
as
stroke
parkinsonism.
believe
this
review
will
provide
strategic
directions
set
standards
leaders
dementia,
governmental
bodies
around
world
coordinating
emergency
response
plans
protecting
caring
amid
COIVD-19
outbreak,
is
likely
continue
at
varying
severity
regions
medium
term.
Molecular Neurodegeneration,
Journal Year:
2020,
Volume and Issue:
15(1)
Published: Nov. 4, 2020
Abstract
Investigations
of
apolipoprotein
E
(
APOE
)
gene,
the
major
genetic
risk
modifier
for
Alzheimer’s
disease
(AD),
have
yielded
significant
insights
into
pathogenic
mechanism.
Among
three
common
coding
variants,
APOE*ε4
increases,
whereas
APOE*ε2
decreases
late-onset
AD
compared
with
APOE*ε3
.
Despite
increased
understanding
detrimental
effect
,
it
remains
unclear
how
confers
protection
against
AD.
Accumulating
evidence
suggests
that
protects
through
both
amyloid-β
(Aβ)-dependent
and
independent
mechanisms.
In
addition,
has
been
identified
as
a
longevity
suggesting
systemic
on
aging
process.
However,
is
not
entirely
benign;
carriers
exhibit
certain
cerebrovascular
diseases
neurological
disorders.
Here,
we
review
from
human
animal
studies
demonstrating
protective
propose
working
model
depicting
potential
underlying
Finally,
discuss
therapeutic
strategies
designed
to
leverage
APOE2
treat
Journal of Clinical Investigation,
Journal Year:
2020,
Volume and Issue:
131(1)
Published: Sept. 29, 2020
Dysfunction
of
immune
and
vascular
systems
has
been
implicated
in
aging
Alzheimer
disease;
however,
their
interrelatedness
remains
poorly
understood.
The
complement
pathway
is
a
well-established
regulator
innate
immunity
the
brain.
Here,
we
report
robust
age-dependent
increases
inflammation,
peripheral
lymphocyte
infiltration,
blood-brain
barrier
(BBB)
permeability.
These
phenotypes
were
subdued
by
global
inactivation
endothelial
cell–specific
ablation
C3ar1.
Using
an
vitro
model
BBB,
identified
intracellular
Ca2+
as
downstream
effector
C3a/C3aR
signaling
functional
mediator
cadherin
junction
integrity.
Endothelial
C3ar1
also
dampened
microglia
reactivity
improved
hippocampal
cortical
volumes
brain,
demonstrating
crosstalk
between
brain
vasculature
dysfunction
cell
activation
neurodegeneration.
Further,
prominent
C3aR-dependent
inflammation
was
observed
tau-transgenic
mouse
model.
Our
studies
suggest
that
heightened
through
cells
promotes
BBB
contributes
to
overall
neuroinflammation
neurodegenerative
disease.
