Journal of Neuroinflammation,
Journal Year:
2025,
Volume and Issue:
22(1)
Published: March 3, 2025
Abstract
Alzheimer’s
disease
(AD)
is
the
most
common
neurodegenerative
worldwide.
Amyloid-β
(Aβ)
accumulation
and
neurofibrillary
tangles
are
two
key
histological
features
resulting
in
progressive
irreversible
neuronal
loss
cognitive
decline.
The
macrophages
of
central
nervous
system
(CNS)
belong
to
innate
immune
comprise
parenchymal
microglia
CNS-associated
(CAMs)
at
CNS
interfaces
(leptomeninges,
perivascular
space
choroid
plexus).
Microglia
CAMs
have
received
attention
as
they
may
play
a
role
onset
progression
e.
g.,
by
clearing
amyloid
beta
through
phagocytosis.
Genome-wide
association
studies
(GWAS)
revealed
that
human
express
numerous
risk
genes
for
AD,
further
highlighting
their
potentially
critical
AD
pathogenesis.
tightly
controlled
environmental
factors,
such
host
microbiota.
Notably,
it
was
reported
composition
gut
microbiota
differed
between
patients
healthy
individuals.
Hence,
emerging
analyzed
impact
bacteria
different
preclinical
mouse
models
well
clinical
studies,
enabling
promising
new
therapeutic
options.
Molecular Neurodegeneration,
Journal Year:
2025,
Volume and Issue:
20(1)
Published: March 14, 2025
Abstract
Alzheimer’s
disease
(AD)
is
neuropathologically
characterized
by
the
extracellular
deposition
of
amyloid-β
peptide
(Aβ)
and
intraneuronal
accumulation
abnormal
phosphorylated
tau
(τ)-protein
(p-τ).
Most
frequently,
these
hallmark
lesions
are
accompanied
other
co-pathologies
in
brain
that
may
contribute
to
cognitive
impairment,
such
as
vascular
lesions,
transactive-response
DNA-binding
protein
43
(TDP-43),
and/or
α-synuclein
(αSyn)
aggregates.
To
estimate
extent
AD
patients,
several
biomarkers
have
been
developed.
Specific
tracers
target
visualize
Aβ
plaques,
p-τ
αSyn
pathology
or
inflammation
positron
emission
tomography.
In
addition
imaging
biomarkers,
cerebrospinal
fluid,
blood-based
biomarker
assays
reflecting
AD-specific
non-specific
processes
either
already
clinical
use
development.
this
review,
we
will
introduce
pathological
brain,
related
discuss
what
respective
determined
at
post-mortem
histopathological
analysis.
It
became
evident
initial
stages
plaque
not
detected
with
currently
available
biomarkers.
Interestingly,
precedes
deposition,
especially
beginning
when
unable
detect
it.
Later,
takes
lead
accelerates
pathology,
fitting
well
known
evolution
measures
over
time.
Some
still
lack
clinically
established
today,
TDP-43
cortical
microinfarcts.
summary,
specific
for
AD-related
pathologies
allow
accurate
diagnosis
based
on
pathobiological
parameters.
Although
current
excellent
pathologies,
they
fail
which
analysis
required.
Accordingly,
neuropathological
studies
remain
essential
understand
development
early
stages.
Moreover,
there
an
urgent
need
co-pathologies,
limbic
predominant,
age-related
encephalopathy-related
modify
interacting
p-τ.
Novel
approaches
vesicle-based
cryptic
RNA/peptides
help
better
future.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(22), P. 11941 - 11941
Published: Nov. 6, 2024
The
identification
of
neuroinflammation
as
a
critical
factor
in
Alzheimer's
disease
(AD)
has
expanded
the
focus
research
beyond
amyloid-β
and
tau
pathology.
neuroinflammatory
fluid
biomarkers
GFAP,
sTREM2,
YKL-40
have
gained
attention
for
their
potential
early
detection
monitoring
progression.
Plasma
GFAP
demonstrated
promise
predicting
conversion
from
mild
cognitive
impairment
to
AD
dementia,
while
sTREM2
highlights
microglial
activation,
although
there
are
conflicting
results
regarding
its
dynamics
pathogenesis.
Advanced
imaging
techniques,
such
PET
tracers
targeting
TSPO
MAO-B,
also
been
developed
visualize
glial
activation
vivo,
offering
spatial
temporal
insights
into
processes.
However,
clinical
implementation
these
faces
challenges
due
lack
specificity,
many
them
can
be
elevated
other
conditions.
Therapeutic
strategies
emerging,
with
TREM2-targeting
therapies
antidiabetic
drugs
like
GLP-1
receptor
agonists
showing
modulating
activity.
Nevertheless,
complexity
neuroinflammation,
which
encompasses
both
protective
harmful
responses,
necessitates
further
fully
unravel
role
optimize
therapeutic
approaches
AD.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(3), P. 1004 - 1004
Published: Jan. 24, 2025
Alzheimer’s
disease
(AD)
is
a
major
neurodegenerative
dementia,
with
its
complex
pathophysiology
challenging
current
treatments.
Recent
advancements
have
shifted
the
focus
from
traditionally
dominant
amyloid
hypothesis
toward
multifactorial
understanding
of
disease.
Emerging
evidence
suggests
that
while
amyloid-beta
(Aβ)
accumulation
central
to
AD,
it
may
not
be
primary
driver
but
rather
part
broader
pathogenic
process.
Novel
hypotheses
been
proposed,
including
role
tau
protein
abnormalities,
mitochondrial
dysfunction,
and
chronic
neuroinflammation.
Additionally,
gut–brain
axis
epigenetic
modifications
gained
attention
as
potential
contributors
AD
progression.
The
limitations
existing
therapies
underscore
need
for
innovative
strategies.
This
study
explores
integration
machine
learning
(ML)
in
drug
discovery
accelerate
identification
novel
targets
candidates.
ML
offers
ability
navigate
AD’s
complexity,
enabling
rapid
analysis
extensive
datasets
optimizing
clinical
trial
design.
synergy
between
these
themes
presents
promising
future
more
effective
Journal of Aging Research and Lifestyle,
Journal Year:
2025,
Volume and Issue:
14, P. 100002 - 100002
Published: Jan. 1, 2025
Some
patients
undergoing
surgical
procedures
display
long-term
post-surgery
cognitive
impairment
(post-operative
dysfunction;
POCD),
which
may
precipitate
progression
to
dementia.
We
investigated
whether
preoperative
defined
using
specific
tests
(Paired-Associates
Learning
and
Spatial-Span
from
the
Cambridge
Neuropsychological
Test
Automated
Battery,
(CANTAB)
was
associated
with
increased
risk
of
POCD.
N
=
590
>65years
a
matched
control
group
n=114
comprised
final
sample.
Patients
were
classified
as
impaired
if
composite
memory-score
derived
two
CANTAB
test
battery
(spatial
working
memory
paired-associate
learning)
scored
1
SD
below
norms
normative
database.
Risk
developing
POCD
3
months
higher
[odds
ratio
2.048
(95%
CI
1.027
-
4.087)]
for
those
pre-surgical
compared
no
impairment.
This
suggests
that
on
hippocampus-based
tasks
spatial-span
paired-associates
learning
is
in
older
patients.
Metabolites,
Journal Year:
2025,
Volume and Issue:
15(2), P. 128 - 128
Published: Feb. 13, 2025
Background:
Brain
glycogen
is
imperative
for
neuronal
health,
as
it
supports
energy
demands
and
metabolic
processes.
This
review
examines
the
pathways
involved
in
storage
utilization
central
nervous
system,
emphasizing
their
role
both
physiology
pathology.
It
explores
how
alterations
metabolism
contribute
to
neurological
disorders,
including
neurodegenerative
diseases,
epilepsy,
conditions
while
highlighting
bidirectional
interaction
between
neurons
glia
maintaining
brain
homeostasis.
Methods:
A
comprehensive
search
of
articles
published
2015
2025
was
conducted
using
following
databases:
ScienceDirect,
Scopus,
Wiley,
Web
Science,
Medline,
PubMed.
The
selection
relevant
studies
based
on
focus
its
conditions,
with
that
did
not
meet
inclusion
criteria
being
excluded.
Results:
processes
are
subject
rigorous
regulation
by
astrocyte-neuron
interactions,
thereby
ensuring
homeostasis
availability.
dysregulation
mobilization
has
been
implicated
development
synaptic
dysfunction,
excitotoxicity,
neurodegeneration
a
variety
disorders.
For
instance,
aberrant
accumulation
diseases
such
Lafora
disease
associated
severe
neurodegeneration,
impaired
shown
exacerbate
deficits
Alzheimer's
epilepsy.
Conclusions:
Targeting
represents
promising
approach
therapeutic
intervention
However,
translation
these
strategies
human
models
remains
challenging,
particularly
regard
long-term
safety
specificity
glycogen-targeted
therapies.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(7), P. 2906 - 2906
Published: March 23, 2025
Interferon
Regulatory
Factors
(IRFs)
are
critical
modulators
of
immune
and
inflammatory
responses,
yet
their
roles
in
Alzheimer's
disease
(AD)
other
neurodegenerative
disorders
remain
incompletely
understood.
While
IRFs
recognized
for
regulatory
functions
neuroinflammation,
microglial
activation,
neuronal
survival,
dual
as
both
drivers
pathological
inflammation
mediators
neuroprotective
pathways
underscore
a
sophisticated
paradox
disorders.
This
review
aims
to
synthesize
current
evidence
on
IRF-mediated
neuroinflammation
AD
related
diseases,
focusing
the
multifaceted
key
IRF
family
members,
including
IRF1,
IRF3,
IRF7.
We
critically
evaluate
divergent
roles:
IRF1
instance,
exacerbate
neuroinflammatory
cascades
amyloid-beta
(Aβ)
pathology
AD,
whereas
IRF7
may
paradoxically
suppress
under
specific
conditions.
Additionally,
we
explore
dysregulation
Parkinson's
disease,
multiple
sclerosis,
amyotrophic
lateral
Huntington's
emphasizing
shared
distinct
mechanisms
across
Restoring
balance
through
genetic
manipulation,
small-molecule
inhibitors,
or
microbiome-derived
could
attenuate
enhance
Aβ
clearance,
protect
integrity.
Ultimately,
this
work
provides
framework
future
research
harness
signaling
development
precision
therapies
diseases.
Frontiers in Aging Neuroscience,
Journal Year:
2025,
Volume and Issue:
17
Published: March 27, 2025
Alzheimer’s
disease
(AD)
is
a
widespread
neurodegenerative
disorder
and
one
of
the
major
challenges
for
public
health.
Despite
extensive
research,
role
microglia
in
AD
remains
complex
dual.
The
aim
this
review
to
summarize
most
recent
advances
research
regarding
dual
concerning
both
immunomodulation
pathological
progression
by
considering
mechanisms
activation
microglia,
effects
on
Aβ
clearance,
tau
pathology,
impacts
due
genetic
variations
microglial
functions.
Among
these
findings
are
status
M1
M2
phenotypes,
crucial
that
variants
like
TREM2
have
modulating
response
microglia.
This
describes
how
modulation
signaling
pathway
might
be
exploited
therapeutically
treatment
underlines
relevance
personalized
medicine
approach.
