Frontiers in Molecular Neuroscience,
Journal Year:
2023,
Volume and Issue:
16
Published: Nov. 30, 2023
Alzheimer's
disease
(AD)
is
a
central
nervous
system
(CNS)
degenerative
disorder,
caused
by
various
factors
including
β-amyloid
toxicity,
hyperphosphorylation
of
tau
protein,
oxidative
stress,
and
others.
The
dysfunction
microglia
has
been
associated
with
the
onset
advancement
different
neurodevelopmental
neurodegenerative
disorders,
such
as
AD.
gut
mammals
harbors
vast
complex
population
microorganisms,
commonly
referred
to
microbiota.
There's
growing
recognition
that
these
microbes
are
intrinsically
intertwined
mammalian
physiology.
Through
circulation
metabolites,
they
establish
metabolic
symbiosis,
enhance
immune
function,
communication
remote
cells,
those
in
brain.
microbiome
plays
crucial
part
influencing
development
performance
microglia,
indicated
recent
preclinical
studies.
Dysbiosis
intestinal
flora
leads
alterations
transcriptome
regulate
interconversion
subtypes.
This
conversation
explores
research
clarifies
how
bacteria,
their
byproducts,
harmful
elements
affect
activation
characteristics
microglia.
understanding
opens
doors
innovative
microbial-based
therapeutic
strategies
for
early
identification
treatment
goals
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.
iMeta,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 20, 2025
Abstract
A
better
understanding
of
the
characteristic
serum
metabolites
and
microbiota
from
gut
oral
cavity
in
centenarians
could
contribute
to
elucidating
mutual
connections
among
them
would
help
provide
information
achieve
healthy
longevity.
Here,
we
have
recruited
a
total
425
volunteers,
including
145
Suixi
county
—
first
certified
“International
Longevity
Health
Care
Base”
China.
An
integrative
analysis
for
metabolites,
gut,
(aged
100–120)
was
compared
with
those
centenarians'
lineal
relatives
24–86),
elderly
65–88)
young
23–54).
Strikingly
distinct
metabolomic
microbiological
profiles
were
observed
within
centenarian
signature,
longevity
family
aging
underscoring
metabolic
diversity
their
relatives.
Within
between
frail
individuals,
significant
differences
metabolite
compositions
are
observed,
suggesting
that
is
associated
unique
patterns.
Through
an
analysis,
tryptophan
pathway
has
been
revealed
be
important
potential
mechanism
individuals
Specifically,
key
metabolite,
5‐methoxyindoleacetic
acid
(5‐MIAA),
genus
Christensenellaceae
R‐7
group,
it
exhibited
effects
delaying
cell
senescence,
promoting
lifespan,
alleviating
inflammation.
Our
characterization
extensive
remodeling
may
offer
new
scientific
insights
achieving
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 28, 2025
SUMMARY
The
etiology
of
Alzheimer’s
Disease
(AD)
remains
largely
unclear
but
is
likely
driven
by
gene-environment
interactions.
Here,
we
present
a
multi-organ
untargeted
metabolomics
dataset
(2,271
samples)
generated
from
five
tissue
types
in
two
genetic
AD
mouse
models
under
colonized
or
germ-free
conditions,
complemented
shotgun
metagenomics
sequencing
data
(666
samples).
Systems-level
analyses
3xTg
and
5xFAD
mice
reveal
clusters
dysregulated
molecular
classes
across
tissues
including
carnitines,
bile
acids,
B
vitamins,
neurotransmitters.
This
signature,
coupled
with
microbiome
profiles,
suggests
increased
oxidative
stress
via
mitochondrial
dysfunction.
Molecular
feature
tracking
tissueMASST,
mass
spectrometry
search
tool
developed
to
bridge
animal
model
findings
human
data,
identifies
microbially-modulated
phenylacetyl-carnitine
as
positively
associated
aging
cognitive
impairment
studies.
With
hundreds
yet-to-be-characterized
metabolites,
this
public
resource
its
tools
will
aid
future
research
the
pathophysiology
AD.
