International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(7), С. 3399 - 3399
Опубликована: Апрель 5, 2025
Alzheimer's
disease
(AD)
and
frontotemporal
dementia
(FTD)
are
the
most
common
forms
of
globally.
AD
is
characterized
by
accumulation
amyloid-β
(Aβ)
plaques
hyperphosphorylated
tau
in
brain,
leading
to
progressive
memory
loss
cognitive
decline,
significantly
impairing
daily
life.
In
contrast,
FTD
marked
selective
degeneration
frontal
and/or
temporal
lobes,
typically
resulting
profound
changes
personality
social
behavior,
speech
disorders,
psychiatric
symptoms.
Numerous
studies
have
found
microRNAs
(miRNAs)-small,
non-coding
RNA
molecules
that
regulate
gene
expression
post-transcriptionally-to
be
dysregulated
FTD.
As
a
result,
miRNAs
emerged
as
promising
novel
biomarkers
for
these
diseases.
This
review
examines
current
understanding
FTD,
emphasizing
their
potential
accessible,
noninvasive
diagnosing
prevalent
neurodegenerative
disorders.
Pharmacological Reviews,
Год журнала:
2023,
Номер
76(2), С. 199 - 227
Опубликована: Дек. 19, 2023
Abstract
Extracellular
vesicles
(EVs)
have
emerged
as
an
attractive
liquid
biopsy
approach
in
the
diagnosis
and
prognosis
of
multiple
diseases
disorders.
The
feasibility
enriching
specific
subpopulations
EVs
from
biofluids
based
on
their
unique
surface
markers
has
opened
novel
opportunities
to
gain
molecular
insight
various
tissues
organs,
including
brain.
Over
past
decade,
bodily
fluids
been
extensively
studied
for
biomarkers
associated
with
neurological
disorders,
such
Alzheimer9s
disease,
Parkinson9s
schizophrenia,
bipolar
disorder,
major
depressive
substance
use
human
immunodeficiency
virus–associated
neurocognitive
cancer/treatment-induced
neurodegeneration.
These
studies
focused
isolation
cargo
characterization
either
total
or
brain
cells,
neuron-,
astrocyte-,
microglia-,
oligodendrocyte-,
pericyte-,
endothelial-derived
achieve
early
predict
treatment
intervention
outcomes.
findings
these
demonstrated
that
could
serve
a
repetitive
less
invasive
source
valuable
information
supplementing
existing
costly
neuroimaging
techniques
relatively
measures,
like
lumbar
puncture.
However,
initial
excitement
surrounding
blood-based
brain-related
tempered
by
challenges,
lack
central
nervous
system
specificity
EV
markers,
lengthy
protocols,
absence
standardized
procedures
biological
sample
collection,
isolation,
characterization.
Nevertheless,
rapid
advancements
field,
supported
improved
methods
sensitive
assays
characterization,
cell–derived
continue
offer
unparallel
significant
translational
implications
Significance
Statement
present
Characterizing
holds
potential
yield
information,
thereby
significantly
impacting
development
This
paper
reviewed
methodology
employed
isolate
extracellular
derived
cells
biofluids,
utility
enhancing
understanding
neurodegeneration,
challenges
this
research
field.
Journal of Extracellular Vesicles,
Год журнала:
2024,
Номер
13(7)
Опубликована: Июль 1, 2024
Abstract
Gut
microbiome
dysbiosis
is
a
major
contributing
factor
to
several
pathological
conditions.
However,
the
mechanistic
understanding
of
communication
between
gut
microbiota
and
extra‐intestinal
organs
remains
largely
elusive.
Extracellular
vesicles
(EVs),
secreted
by
almost
every
form
life,
including
bacteria,
could
play
critical
role
in
this
inter‐kingdom
crosstalk
are
focus
present
study.
Here,
we
novel
approach
for
isolating
lipopolysaccharide
(LPS)+
bacterial
extracellular
(bEV
LPS
)
from
complex
biological
samples,
faeces,
plasma
liver
lean
diet‐induced
obese
(DIO)
mice.
bEV
were
extensively
characterised
using
nanoparticle
tracking
analyses,
immunogold
labelling
coupled
with
transmission
electron
microscopy,
flow
cytometry,
super‐resolution
microscopy
16S
sequencing.
In
tissues,
protein
expressions
TLR4
few
macrophage‐specific
biomarkers
assessed
immunohistochemistry,
gene
inflammation‐related
cytokines
their
receptors
(
n
=
89
genes)
measured
PCR
array.
Faecal
samples
DIO
mice
revealed
remarkably
lower
concentration
total
EVs
but
significantly
higher
percentage
LPS+
EVs.
Interestingly,
faecal
showed
abundance
Proteobacteria
Importantly,
mice,
number
consistently
entered
hepatic
portal
vein
subsequently
reached
liver,
associated
increased
expression
TLR4,
macrophage
markers
(F4/80,
CD86
CD206),
Il1rn
,
Ccr1
Cxcl10
Il2rg
Ccr2
).
Furthermore,
portion
escaped
peripheral
circulation.
conclusion,
be
key
mediator
orchestrating
various
well‐established
effects
induced
bacteria
on
distant
organs.
Journal of Extracellular Vesicles,
Год журнала:
2024,
Номер
13(1)
Опубликована: Янв. 1, 2024
Abstract
Brain‐derived
extracellular
vesicles
(EVs)
play
an
active
role
in
Alzheimer's
disease
(AD),
relaying
important
physiological
information
about
their
host
tissues.
The
internal
cargo
of
EVs
is
protected
from
degradation,
making
attractive
AD
biomarkers.
However,
it
unclear
how
circulating
relate
to
isolated
disease‐vulnerable
brain
regions.
We
developed
a
novel
method
for
collecting
the
hippocampal
interstitial
fluid
(ISF)
live
mice.
(EV
ISF
)
were
via
ultracentrifugation
and
characterized
by
nanoparticle
tracking
analysis,
immunogold
labelling,
flow
cytometry.
Mass
spectrometry
proteomic
analyses
performed
on
EV
cargo.
40–150
nm
size
expressed
CD63,
CD9,
CD81.
Using
model
cerebral
amyloidosis
(e.g.,
APPswe
,
PSEN1dE9
mice),
we
found
protein
concentration
increased
but
diversity
decreased
with
Aβ
deposition.
Genotype,
age,
deposition
modulated
proteostasis‐
immunometabolic‐related
pathways.
Changes
microglial
proteome
sexually
dimorphic
associated
differential
response
plaque
microglia.
that
female
APP/PS1
mice
have
more
amyloid
plaques,
less
microglia,
robust‐
diverse‐
proteome.
Thus,
vivo
microdialysis
technique
offers
unique
opportunity
explore
AD.
CNS Neuroscience & Therapeutics,
Год журнала:
2024,
Номер
30(3)
Опубликована: Март 1, 2024
Abstract
Background
Accumulation
of
amyloid
beta,
tau
hyperphosphorylation,
and
microglia
activation
are
the
three
highly
acknowledged
pathological
factors
Alzheimer's
disease
(AD).
However,
oligodendrocytes
(OLs)
were
also
widely
investigated
in
pathogenesis
treatment
for
AD.
Aims
We
aimed
to
update
regulatory
targets
differentiation
maturation
OLs,
emphasized
key
role
OLs
occurrence
Methods
This
review
first
concluded
OL
with
AD
pathogenesis,
then
advanced
based
on
both
clinic
basic
experiments.
Later,
we
extensively
discussed
possible
application
current
progress
diagnosis
this
complex
disease.
Results
Molecules
involving
OLs’
or
maturation,
including
various
transcriptional
factors,
cholesterol
homeostasis
regulators,
microRNAs
could
participate
Clinical
data
point
towards
impairment
patients.
Basic
research
further
supports
central
regulation
pathologies.
Additionally,
classic
drugs,
donepezil,
edaravone,
fluoxetine,
clemastine
demonstrate
their
potential
remedying
models,
new
therapeutics
from
perspective
is
constantly
being
developed.
Conclusions
believe
that
dysfunction
one
important
Factors
regulating
might
be
biomarkers
early
agents
stimulating
warrant
development
anti‐AD
drugs.
Acta Neuropathologica Communications,
Год журнала:
2024,
Номер
12(1)
Опубликована: Март 5, 2024
Abstract
Accurate
differential
diagnosis
among
various
dementias
is
crucial
for
effective
treatment
of
Alzheimer’s
disease
(AD).
The
study
began
with
searching
novel
blood-based
neuronal
extracellular
vesicles
(EVs)
that
are
more
enriched
in
the
brain
regions
vulnerable
to
AD
development
and
progression.
With
extensive
proteomic
profiling,
GABRD
GPR162
were
identified
as
regionally
plasma
EVs
markers.
performance
GPR162,
along
molecule
pTau217,
was
tested
using
self-developed
optimized
nanoflow
cytometry-based
technology,
which
not
only
detected
positive
ratio
but
also
concurrently
presented
corresponding
particle
size
EVs,
discovery
(n
=
310)
validation
213)
cohorts.
Plasma
+
-
or
-carrying
pTau217-EVs
significantly
reduced
compared
healthy
control
(HC).
Additionally,
distribution
different
between
non-AD
dementia
(NAD).
An
integrative
model,
combining
age,
number
pTau217-EVs,
accurately
sensitively
discriminated
from
HC
[discovery
cohort,
area
under
curve
(AUC)
0.96;
AUC
0.93]
effectively
differentiated
NAD
(discovery
0.91;
0.90).
This
showed
carrying
pTau217
may
serve
a
robust
diagnostic
tool
both
clinical
practice
trials
AD.
Alzheimer s & Dementia,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 17, 2025
Extracellular
vesicles
(EVs)
have
emerged
as
novel
blood-based
biomarkers
for
various
pathologies.
The
development
of
methods
to
enrich
cell-specific
EVs
from
biofluids
has
enabled
us
monitor
difficult-to-access
organs,
such
the
brain,
in
real
time
without
disrupting
their
function,
thus
serving
liquid
biopsy.
Burgeoning
evidence
indicates
that
contents
neuron-derived
(NDEs)
blood
reveal
dynamic
alterations
occur
during
neurodegenerative
pathogenesis,
including
Alzheimer's
disease
(AD),
reflecting
a
disease-specific
molecular
signature.
Among
these
AD-specific
changes
is
brain
insulin-signaling
dysregulation,
which
cannot
be
assessed
clinically
living
patient
and
remains
an
unexplained
co-occurrence
AD
pathogenesis.
This
review
focused
on
delineating
how
NDEs
may
begin
close
gap
between
identifying
associated
with
insulin
dysregulation
reliably
patients
its
connection
AD.
approach
could
lead
identification
early
less-invasive
diagnostic
HIGHLIGHTS:
Neuron-derived
extracellular
isolated
peripheral
blood.
reflect
signature
(AD).
Brain
plays
critical
role
predict
dysregulation.
offer
