JAMA Neurology,
Journal Year:
2016,
Volume and Issue:
74(1), P. 91 - 91
Published: Nov. 28, 2016
Importance
Cognitive
impairment
and
dementia,
including
Alzheimer
disease
(AD),
are
common
within
the
aging
population,
yet
factors
that
render
brain
vulnerable
to
these
processes
unknown.
Perivascular
localization
of
aquaporin-4
(AQP4)
facilitates
clearance
interstitial
solutes,
amyloid-β,
through
brainwide
network
perivascular
pathways
termed
theglymphatic
system,
which
may
be
compromised
in
brain.
Objectives
To
determine
whether
alterations
AQP4
expression
or
loss
features
human
define
their
association
with
AD
pathology.
Design,
Setting,
Participants
Expression
was
analyzed
postmortem
frontal
cortex
cognitively
healthy
histopathologically
confirmed
individuals
by
Western
blot
immunofluorescence
for
AQP4,
amyloid-β
1-42,
glial
fibrillary
acidic
protein.
Postmortem
tissue
clinical
data
were
provided
Oregon
Health
Science
University
Layton
Aging
Disease
Center
Brain
Bank.
from
79
evaluated,
intact
“young”
aged
younger
than
60
years
(range,
33-57
years),
“aged”
older
61-96
years)
no
known
neurological
disease,
61-105
age
a
history
histopathological
evaluation.
Forty-eight
patient
samples
(10
young,
20
aged,
18
AD)
underwent
histological
analysis.
Sixty
analysis
(15
24
21
AD).
Main
Outcomes
Measures
protein,
immunoreactivity,
evaluated.
Results
associated
advancing
among
all
(R2
=
0.17;P
.003).
significantly
status
independent
(OR,
11.7
per
10%
increase
localization;
z
−2.89;P
.004)
preserved
eldest
85
who
remained
intact.
When
controlling
age,
increased
burden
0.15;P
.003)
increasing
Braak
stage
0.14;P
.006).
Conclusions
Relevance
In
this
study,
altered
brains.
Loss
factor
renders
misaggregation
proteins,
such
as
neurodegenerative
conditions
AD.
Physiological Reviews,
Journal Year:
2018,
Volume and Issue:
99(1), P. 21 - 78
Published: Oct. 3, 2018
The
blood-brain
barrier
(BBB)
prevents
neurotoxic
plasma
components,
blood
cells,
and
pathogens
from
entering
the
brain.
At
same
time,
BBB
regulates
transport
of
molecules
into
out
central
nervous
system
(CNS),
which
maintains
tightly
controlled
chemical
composition
neuronal
milieu
that
is
required
for
proper
functioning.
In
this
review,
we
first
examine
molecular
cellular
mechanisms
underlying
establishment
BBB.
Then,
focus
on
physiology,
endothelial
pericyte
transporters,
perivascular
paravascular
transport.
Next,
discuss
rare
human
monogenic
neurological
disorders
with
primary
genetic
defect
in
BBB-associated
cells
demonstrating
link
between
breakdown
neurodegeneration.
review
effects
genes
inheritance
and/or
increased
susceptibility
Alzheimer's
disease
(AD),
Parkinson's
(PD),
Huntington's
disease,
amyotrophic
lateral
sclerosis
(ALS)
relation
to
other
pathologies
deficits.
We
next
how
dysfunction
relates
deficits
majority
sporadic
AD,
PD,
ALS
cases,
multiple
sclerosis,
neurodegenerative
disorders,
acute
CNS
such
as
stroke,
traumatic
brain
injury,
spinal
cord
epilepsy.
Lastly,
BBB-based
therapeutic
opportunities.
conclude
lessons
learned
future
directions,
emphasis
technological
advances
investigate
functions
living
brain,
at
level,
address
key
unanswered
questions.
Molecular Psychiatry,
Journal Year:
2021,
Volume and Issue:
26(10), P. 5481 - 5503
Published: Aug. 30, 2021
Abstract
Breakthroughs
in
molecular
medicine
have
positioned
the
amyloid-β
(Aβ)
pathway
at
center
of
Alzheimer’s
disease
(AD)
pathophysiology.
While
detailed
mechanisms
and
spatial-temporal
dynamics
leading
to
synaptic
failure,
neurodegeneration,
clinical
onset
are
still
under
intense
investigation,
established
biochemical
alterations
Aβ
cycle
remain
core
biological
hallmark
AD
promising
targets
for
development
disease-modifying
therapies.
Here,
we
systematically
review
update
vast
state-of-the-art
literature
science
with
evidence
from
basic
research
studies
human
genetic
multi-modal
biomarker
investigations,
which
supports
a
crucial
role
dyshomeostasis
pathophysiological
dynamics.
We
discuss
highlighting
differentiated
interaction
distinct
species
other
AD-related
mechanisms,
such
as
tau-mediated,
neuroimmune
inflammatory
changes,
well
neurochemical
imbalance.
Through
lens
latest
multimodal
vivo
biomarkers
AD,
this
cross-disciplinary
examines
compelling
hypothesis-
data-driven
rationale
Aβ-targeting
therapeutic
strategies
early
treatment
AD.
