Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
181, P. 117718 - 117718
Published: Dec. 1, 2024
Behavioral
testing
is
an
essential
tool
for
evaluating
cognitive
function
and
dysfunction
in
preclinical
research
models.
This
of
special
importance
the
study
neurological
disorders
such
as
Alzheimer's
disease.
However,
reproducibility
classic
behavioral
assays
frequently
compromised
by
interstudy
variation,
leading
to
ambiguous
conclusions
about
markers
characterizing
Here,
we
identify
age-
genotype-driven
differences
between
3xTg-AD
non-transgenic
control
mice
using
a
low-cost,
highly
customizable
assay
that
requires
little
human
intervention.
Through
phenotyping
combining
both
supervised
unsupervised
classification
methods,
are
able
validate
preventative
effects
immunosuppressant
cyclosporine
A
rodent
model
disease,
well
partially
ameliorating
candidate
drugs
nebivolol
cabozantinib.
Aging Cell,
Journal Year:
2024,
Volume and Issue:
23(5)
Published: Feb. 15, 2024
Cerebrovascular
dysfunction
has
been
implicated
as
a
major
contributor
to
Alzheimer's
Disease
(AD)
pathology,
with
cerebral
endothelial
cell
(cEC)
stress
promoting
ischemia,
cerebral-blood
flow
impairments
and
blood-brain
barrier
(BBB)
permeability.
Recent
evidence
suggests
that
cardiovascular
(CV)/cerebrovascular
risk
factors,
including
hyperhomocysteinemia
(Hhcy),
exacerbate
AD
pathology
risk.
Yet,
the
underlying
molecular
mechanisms
for
this
interaction
remain
unclear.
Our
lab
demonstrated
amyloid
beta
40
(Aβ40)
species,
particularly
Aβ40-E22Q
(AβQ22;
vasculotropic
Dutch
mutant),
promote
death
receptor
4
5
(DR4/DR5)-mediated
apoptosis
in
human
cECs,
permeability,
angiogenic
impairment.
Previous
studies
show
Hhcy
also
induces
EC
dysfunction,
but
it
remains
unknown
whether
Aβ
homocysteine
function
through
common
mechanisms.
We
tested
hypotheses
exacerbates
Aβ-induced
cEC
DR4/5-mediated
apoptosis,
angiogenesis
defects.
This
study
was
first
demonstrate
specifically
potentiates
AβQ22-mediated
activation
of
extrinsic
apoptotic
pathway
DR4/5
expression,
caspase
8/9/3
activation,
cytochrome-c
release
DNA
fragmentation.
Additionally,
we
revealed
intensifies
deregulation
same
junction
proteins
mediated
by
Aβ,
precipitating
BBB
Furthermore,
AβQ22,
impairing
VEGF-A/VEGFR2
signaling
VEGFR2
endosomal
trafficking,
additively
decrease
capabilities.
Overall,
these
results
presence
CV
factor
reveals
specific
which
amyloidosis
jointly
operate
produce
brain
death,
highlighting
new
potential
targets
against
vascular
comorbid
AD/CAA
conditions.
Frontiers in Physiology,
Journal Year:
2023,
Volume and Issue:
14
Published: Jan. 30, 2023
The
heart
is
a
functional
syncytium
controlled
by
delicate
and
sophisticated
balance
ensured
the
tight
coordination
of
its
several
cell
subpopulations.
Accordingly,
cardiomyocytes
together
with
surrounding
microenvironment
participate
in
tissue
homeostasis.
In
right
atrium,
sinoatrial
nodal
cells
regulate
cardiac
impulse
propagation
through
cardiomyocytes,
thus
ensuring
maintenance
electric
network
tissue.
Notably,
central
nervous
system
(CNS)
modulates
rhythm
two
limbs
autonomic
(ANS):
parasympathetic
sympathetic
compartments.
exerts
non-voluntary
effects
on
different
peripheral
organs.
main
neuromodulator
Sympathetic
Nervous
System
(SNS)
norepinephrine,
while
principal
neurotransmitter
Parasympathetic
(PNS)
acetylcholine.
Through
these
neurohormones,
ANS
can
gradually
cardiac,
vascular,
visceral,
glandular
functions
turning
one
branches
(adrenergic
and/or
cholinergic),
which
exert
opposite
targeted
Besides
neuromodulators,
ruled
specific
neuropeptides
(neurotrophic
factors)
that
help
to
preserve
innervation
homeostasis
myocardial
layers
(from
epicardium
endocardium).
Interestingly,
dysregulation
this
neuro-signaling
pathway
may
expose
severe
disorders
etiology
nature.
Specifically,
maladaptive
remodeling
culminate
progressive
loss
neurotrophins,
leading
denervation,
as
observed
cardiometabolic
neurodegenerative
diseases
(myocardial
infarction,
failure,
Alzheimer's
disease).
This
review
analyzes
current
knowledge
pathophysiological
processes
involved
impairment
from
perspectives
both
widely
diffused
devastating
disorder,
disease,
proposing
relationship
between
neurodegeneration,
neurotrophic
factors,
impairment.
overview
conducive
more
comprehensive
understanding
process
dysfunction,
bringing
light
potential
therapeutic
scenarios
correct
or
delay
adverse
cardiovascular
remodeling,
improving
prognosis
quality
life
patients
disorders.
Nutrients,
Journal Year:
2023,
Volume and Issue:
15(21), P. 4662 - 4662
Published: Nov. 3, 2023
As
aging
societies
in
the
western
world
face
a
growing
prevalence
of
vascular
cognitive
impairment
and
Alzheimer's
disease
(AD),
understanding
their
underlying
causes
associated
risk
factors
becomes
increasingly
critical.
A
salient
concern
dietary
context
is
high
consumption
methionine-rich
foods
such
as
red
meat.
The
present
review
delves
into
impact
this
methionine-heavy
diet
resultant
hyperhomocysteinemia
on
accelerated
cerebrovascular
brain
aging,
emphasizing
potential
roles
impairment.
Through
comprehensive
exploration
existing
evidence,
link
between
methionine
intake
oxidative
stress,
mitochondrial
dysfunction,
inflammation,
epigenetic
drawn.
Moreover,
microvascular
determinants
deterioration,
including
endothelial
reduced
cerebral
blood
flow,
rarefaction,
impaired
neurovascular
coupling,
blood-brain
barrier
(BBB)
disruption,
are
explored.
mechanisms
by
which
excessive
might
drive
cerebromicrovascular
processes
elucidated.
By
presenting
an
intricate
relationships
among
diets,
hyperhomocysteinemia,
impairment,
avenues
for
future
research
therapeutic
interventions
suggested.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(4), P. 786 - 786
Published: April 3, 2024
The
escalating
prevalence
of
Alzheimer's
disease
(AD)
highlights
the
urgent
need
to
develop
reliable
biomarkers
for
early
diagnosis
and
intervention.
AD
is
characterized
by
pathological
accumulation
amyloid-beta
plaques
tau
neurofibrillary
tangles.
Phosphorylated
(p-tau)
proteins,
particularly
p-tau217
p-tau231,
have
been
identified
as
promising
biomarker
candidates
differentiate
progression
from
preclinical
stages.
This
narrative
review
devoted
a
critical
evaluation
diagnostic
accuracy,
sensitivity,
specificity
p-tau231
levels
in
detection
AD,
measured
plasma,
serum,
cerebrospinal
fluid,
compared
established
biomarkers.
Additionally,
efficacy
these
markers
distinguishing
other
neurodegenerative
disorders
examined.
significant
advances
offered
diagnostics
are
highlighted,
demonstrating
their
unique
utility
differential
diagnosis.
comprehensive
analysis
not
only
confirms
excellent
capabilities
markers,
but
also
deepens
understanding
molecular
dynamics
contributing
broader
scientific
discourse
on
diseases.
aimed
provide
key
information
researchers
clinicians
across
disciplines,
filling
interdisciplinary
gaps
highlighting
role
p-tau
proteins
revolutionizing
research
clinical
practice.
ACS Omega,
Journal Year:
2023,
Volume and Issue:
8(39), P. 36025 - 36031
Published: Sept. 19, 2023
We
previously
demonstrated
that
serum
levels
of
plasminogen
activator
inhibitor-1
(PAI-1),
which
inhibits
both
the
tissue
(tPA)
and
plasmin
activity,
are
increased
in
patients
with
Alzheimer's
disease.
tPA/plasmin
not
only
prevents
accumulation
β-amyloid
brain
but
also
is
involved
synthesis
brain-derived
neurotrophic
factor
(BDNF),
a
neurotrophin
whose
reduced
Alzheimer.
In
present
study,
we
compared
BDNF
Alzheimer
dementia
to
those
amnestic
mild
cognitive
impairment
cognitively
healthy
controls.
Moreover,
examined
whether
PAI-1/BDNF
ratio
correlates
disease
severity,
as
measured
by
Mini-Mental
State
Examination.
Our
results
showed
lower
(13.7%
less)
PAI-1
higher
than
(23%
more)
or
controls
(36%
more).
Furthermore,
was
significantly
(36.4%
(40%
Lastly,
negatively
correlated
score.
suggest
Alzheimer,
impairing
production
BDNF,
implicated
progression.
They
indicate
could
be
used
marker
support
this
hypothesis,
strong
negative
correlation
between
score
observed.
American Journal of Hypertension,
Journal Year:
2024,
Volume and Issue:
37(7), P. 493 - 502
Published: April 4, 2024
Abstract
BACKGROUND
The
prevalence
of
many
chronic
conditions
has
increased
among
US
adults.
Many
adults
with
hypertension
have
other
conditions.
METHODS
We
estimated
changes
in
the
age-adjusted
multiple
(≥3)
conditions,
not
including
hypertension,
using
data
from
National
Health
and
Nutrition
Examination
Survey,
1999–2000
to
2017–2020,
(n
=
24,851)
without
24,337
hypertension.
Hypertension
included
systolic
blood
pressure
(BP)
≥130
mm
Hg,
diastolic
BP
≥80
or
antihypertensive
medication
use.
studied
14
conditions:
arthritis,
asthma,
cancer,
coronary
heart
disease,
kidney
depression,
diabetes,
dyslipidemia,
hepatitis
B,
C,
failure,
lung
obesity,
stroke.
RESULTS
From
mean
number
more
vs.
(2.2
2.8
1.7
2.0;
P-interaction
<0.001).
Also,
39.0%
52.0%
26.0%
30.0%
(P-interaction
0.022).
In
after
age,
gender,
race/ethnicity
adjustment,
were
1.94
(95%
confidence
interval:
1.72–2.18)
times
as
likely
compared
those
arthritis
most
common
3
co-occurring
(age-adjusted
16.5%
3.1%,
respectively).
CONCLUSIONS
than
half
had
≥3
additional
a
substantial
increase
20
years
ago.
