Experimental Brain Research,
Год журнала:
2024,
Номер
242(3), С. 543 - 557
Опубликована: Янв. 11, 2024
Abstract
Apolipoprotein
E
ε4
allele
(APOE4)
is
the
predominant
genetic
risk
factor
for
late-onset
Alzheimer’s
disease
(AD).
APOE4
mouse
models
have
provided
advances
in
understanding
of
pathogenesis,
but
unaccounted
variables
like
rodent
housing
status
may
hinder
translational
outcomes.
Non-sterile
aspects
food
and
bedding
can
be
major
sources
changes
microflora.
Alterations
intestinal
microbial
ecology
cause
mucosal
barrier
impairment
increase
pro-inflammatory
signals.
The
present
study
examined
role
sterile
non-sterile
on
redox
indicators
immune
humanized-
knock-in
mice
(hAPOe4).
hAPOE4
were
housed
under
conditions
until
22
months
age,
followed
by
transfer
a
cohort
to
2
months.
At
24
redox/immunologic
was
evaluated
flow
cytometry/ELISA.
females
exhibited:
(1)
higher
neuronal
microglial
oxygen
radical
production
(2)
lower
CD68
+
microglia
(brain)
CD8
T
cells
(periphery)
compared
sterile-housed
mice.
In
contrast,
males
MHCII
CD11b
CD4
levels
lipopolysaccharide-binding
protein
inflammatory
cytokines
periphery
relative
This
demonstrated
that
vs.
are
associated
with
activation
responses
brain
sex-dependent
manner.
Therefore,
contribute
variable
outcomes
both
periphery.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Авг. 23, 2024
Abstract
Alzheimer’s
disease
(AD)
stands
as
the
predominant
form
of
dementia,
presenting
significant
and
escalating
global
challenges.
Its
etiology
is
intricate
diverse,
stemming
from
a
combination
factors
such
aging,
genetics,
environment.
Our
current
understanding
AD
pathologies
involves
various
hypotheses,
cholinergic,
amyloid,
tau
protein,
inflammatory,
oxidative
stress,
metal
ion,
glutamate
excitotoxicity,
microbiota-gut-brain
axis,
abnormal
autophagy.
Nonetheless,
unraveling
interplay
among
these
pathological
aspects
pinpointing
primary
initiators
require
further
elucidation
validation.
In
past
decades,
most
clinical
drugs
have
been
discontinued
due
to
limited
effectiveness
or
adverse
effects.
Presently,
available
primarily
offer
symptomatic
relief
often
accompanied
by
undesirable
side
However,
recent
approvals
aducanumab
(
1
)
lecanemab
2
Food
Drug
Administration
(FDA)
present
potential
in
disrease-modifying
Nevertheless,
long-term
efficacy
safety
need
Consequently,
quest
for
safer
more
effective
persists
formidable
pressing
task.
This
review
discusses
pathogenesis,
advances
diagnostic
biomarkers,
latest
updates
trials,
emerging
technologies
drug
development.
We
highlight
progress
discovery
selective
inhibitors,
dual-target
allosteric
modulators,
covalent
proteolysis-targeting
chimeras
(PROTACs),
protein-protein
interaction
(PPI)
modulators.
goal
provide
insights
into
prospective
development
application
novel
drugs.
Frontiers in Aging Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Авг. 21, 2024
Introduction
Alzheimer’s
disease
(AD),
a
major
cause
of
dementia
globally,
imposes
significant
societal
and
personal
costs.
This
review
explores
the
efficacy
physical
exercise
as
non-pharmacological
intervention
to
mitigate
impacts
AD.
Methods
draws
on
recent
studies
that
investigate
effects
neuroinflammation
neuronal
enhancement
in
individuals
with
Results
Consistent
alters
neuroinflammatory
pathways,
enhances
cognitive
functions,
bolsters
brain
health
among
AD
patients.
It
favorably
influences
activation
states
microglia
astrocytes,
fortifies
integrity
blood-brain
barrier,
attenuates
gut
inflammation
associated
These
changes
are
substantial
improvements
performance
indicators.
Discussion
The
findings
underscore
potential
integrating
into
comprehensive
management
strategies.
Emphasizing
necessity
for
further
research,
this
advocates
refinement
regimens
maximize
their
enduring
benefits
decelerating
progression
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(20), С. 11272 - 11272
Опубликована: Окт. 19, 2024
Recent
studies
underscore
the
role
of
gut
and
oral
microbiota
in
influencing
neuroinflammation
through
microbiota–gut–brain
axis,
including
Alzheimer’s
disease
(AD).
This
review
aims
to
provide
a
comprehensive
synthesis
recent
findings
on
involvement
neuroinflammatory
processes
associated
with
AD,
emphasizing
novel
insights
therapeutic
implications.
reveals
that
dysbiosis
AD
patients’
is
linked
heightened
peripheral
central
inflammatory
responses.
Specific
bacterial
taxa,
such
as
Bacteroides
Firmicutes
gut,
well
Porphyromonas
gingivalis
cavity,
are
notably
altered
leading
significant
changes
microglial
activation
cytokine
production.
Gut
alterations
increased
intestinal
permeability,
facilitating
translocation
endotoxins
like
lipopolysaccharides
(LPS)
into
bloodstream
exacerbating
by
activating
brain’s
toll-like
receptor
4
(TLR4)
pathways.
Furthermore,
microbiota-derived
metabolites,
short-chain
fatty
acids
(SCFAs)
amyloid
peptides,
can
cross
blood-brain
barrier
modulate
While
microbial
amyloids
may
contribute
amyloid-beta
aggregation
brain,
certain
SCFAs
butyrate
exhibit
anti-inflammatory
properties,
suggesting
potential
avenue
mitigate
neuroinflammation.
not
only
highlights
critical
pathology
but
also
offers
ray
hope
modulating
could
represent
strategy
for
reducing
slowing
progression.
Intrinsic
capacity
is
a
crucial
indicator
of
adverse
outcomes
and
has
predictive
value
for
diseases
mortality.
The
objective
this
study
to
assess
the
association
between
nighttime
sleep
duration
intrinsic
in
older
Chinese
adults.
Data
were
collected
from
China
Health
Retirement
Longitudinal
Study
(CHARLS)
spanning
years
2008–2020.
Minimally
sufficient
adjustment
was
made
confounding
factors
identified
through
Directed
Acyclic
Graphs
(DAGs),
multivariate
logistic
regression
analysis
conducted
determine
relationship
capacity.
Restricted
cubic
splines
(RCS)
used
nonlinear
population.
Finally,
subgroup
interaction
effect
performed.
Among
4994
adults,
3118
(62.4%)
experienced
decline
After
adjusting
factors,
associated
with
an
increased
risk
(P
<
0.001),
exhibiting
J-shaped
pattern.
For
shows
nonlinear,
dose-response
decline.
Our
provides
important
insights
into
health
self-management
Regenerative Biomaterials,
Год журнала:
2024,
Номер
11
Опубликована: Янв. 1, 2024
Abstract
The
intricate
nature
of
oral-maxillofacial
structure
and
function,
coupled
with
the
dynamic
oral
bacterial
environment,
presents
formidable
obstacles
in
addressing
repair
regeneration
bone
defects.
Numerous
characteristics
should
be
noticed
repair,
such
as
irregular
morphology
defects,
homeostasis
between
hosts
microorganisms
cavity
complex
periodontal
structures
that
facilitate
epithelial
ingrowth.
Therefore,
necessitates
restoration
materials
adhere
to
stringent
specific
demands.
This
review
starts
exploring
these
particular
requirements
by
introducing
bones
then
summarizes
classifications
current
respect
composition
structure.
Additionally,
we
discuss
modifications
including
improving
mechanical
properties,
optimizing
surface
topography
pore
adding
bioactive
components
elements,
compounds,
cells
their
derivatives.
Ultimately,
organize
a
range
potential
optimization
strategies
future
perspectives
for
enhancing
materials,
physical
environment
manipulation,
microbial
modulation,
osteo-immune
regulation,
smart
stimuli-responsive
multifaceted
approach
poly-pathic
treatment,
hope
providing
some
insights
researchers
this
field.
In
summary,
analyzes
demands
especially
alveolar
bone,
concludes
corresponding
biomaterials
aims
inspire
research
pursuit
more
effective
treatment
outcomes.
Frontiers in Endocrinology,
Год журнала:
2024,
Номер
15
Опубликована: Сен. 4, 2024
Alzheimer's
Disease
(AD)
is
increasingly
recognized
as
being
associated
with
metabolic
disorders,
including
Metabolic
Associated
Steatotic
Liver
(MASLD).
This
study
aimed
to
assess
the
relative
risk
of
AD
in
individuals
MASLD.
Microorganisms,
Год журнала:
2025,
Номер
13(1), С. 122 - 122
Опубликована: Янв. 9, 2025
Alzheimer's
disease
(AD),
the
most
common
form
of
dementia,
is
a
progressive
neurodegenerative
disorder
that
profoundly
impacts
cognitive
function
and
nervous
system.
Emerging
evidence
highlights
pivotal
roles
iron
homeostasis
dysregulation
microbial
inflammatory
factors
in
oral
gut
microbiome
as
potential
contributors
to
pathogenesis
AD.
Iron
disruption
can
result
excessive
intracellular
accumulation,
promoting
generation
reactive
oxygen
species
(ROS)
oxidative
damage.
Additionally,
agents
produced
by
pathogenic
bacteria
may
enter
body
via
two
primary
pathways:
directly
through
or
indirectly
cavity,
entering
bloodstream
reaching
brain.
This
infiltration
disrupts
cellular
homeostasis,
induces
neuroinflammation,
exacerbates
AD-related
pathology.
Addressing
these
mechanisms
personalized
treatment
strategies
target
underlying
causes
AD
could
play
critical
role
preventing
its
onset
progression.
Journal of Dental Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 4, 2025
Porphyromonas
gingivalis
is
one
of
the
major
pathogens
chronic
periodontitis.
P.
can
cause
systemic
inflammation,
amyloid
β
protein
deposition,
and
hyperphosphorylation
tau
protein,
leading
to
Alzheimer’s
disease
(AD)–like
lesions.
oral
infection
causes
gut
microbiota
alteration,
barrier
dysfunction,
intestinal
immune
response
inflammation.
The
microbiota-gut-brain
axis
has
a
potential
role
in
pathogenesis
AD.
Whether
affects
AD-like
lesions
via
gut-brain
needs
more
study.
In
this
study,
orally
administered
induced
alveolar
resorption,
impairment,
Oral
with
microflora
dysbiosis,
imbalance
tryptophan
metabolism
pathway
microbiota,
elevated
levels
3-hydroxykynurenine
sera
hippocampi.
key
metabolite,
3-hydroxykynurenine,
suppressed
Bcl2
gene
expression,
neuronal
apoptosis
promoting
vivo
vitro.
These
findings
suggest
that
induce
AD
through
axis,
providing
new
ideas
for
prevention
treatment
