Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Дек. 20, 2023
Abstract
There
is
extensive
synaptic
loss
from
frontotemporal
lobar
degeneration,
in
preclinical
models
and
human
vivo
post
mortem
studies.
Understanding
the
consequences
of
for
network
function
important
to
support
translational
guide
future
therapeutic
strategies.
To
examine
this
relationship,
we
recruited
55
participants
with
syndromes
associated
degeneration
24
healthy
controls.
We
measured
density
positron
emission
tomography
using
radioligand
[
11
C]UCB-J,
which
binds
presynaptic
vesicle
glycoprotein
SV2A,
neurite
dispersion
diffusion
magnetic
resonance
imaging,
task-free
imaging
functional
connectivity.
Synaptic
patients
was
reduced
connectivity
beyond
atrophy.
Functional
moderated
relationship
between
clinical
severity.
Our
findings
confirm
importance
syndromes,
resulting
effect
on
behaviour
as
a
abnormal
Biomedicines,
Год журнала:
2023,
Номер
11(2), С. 355 - 355
Опубликована: Янв. 26, 2023
Early
cognitive
decline
in
patients
with
Alzheimer's
(AD)
is
associated
quantifiable
structural
and
functional
connectivity
changes
the
brain.
AD
dysregulation
of
Aβ
tau
metabolism
progressively
disrupt
normal
synaptic
function,
leading
to
loss
synapses,
decreased
hippocampal
density
early
atrophy.
Advances
brain
imaging
techniques
living
have
enabled
transition
from
clinical
signs
symptoms-based
diagnosis
biomarkers-based
diagnosis,
techniques,
quantitative
EEG,
body
fluids
sampling.
The
hippocampus
has
a
central
role
semantic
episodic
memory
processing.
This
function
critically
dependent
on
intrahippocampal
connections
many
cortical
regions,
including
perirhinal
entorhinal
cortex,
parahippocampal
association
regions
temporal
parietal
lobes,
prefrontal
cortex.
Therefore,
reflected
altered
intrinsic
networks
(aka
large-scale
networks),
memory,
default
mode,
salience
networks.
narrative
review
discusses
recent
critical
issues
related
detecting
AD-associated
markers
high-risk
or
neuropsychologically
diagnosed
subjective
impairment
mild
impairment.
Ageing Research Reviews,
Год журнала:
2024,
Номер
94, С. 102197 - 102197
Опубликована: Янв. 22, 2024
Positron
emission
tomography
(PET)
with
radiotracers
that
bind
to
synaptic
vesicle
glycoprotein
2
A
(SV2A)
enables
quantification
of
density
in
the
living
human
brain.
Assessing
regional
distribution
and
severity
loss
will
contribute
our
understanding
pathological
processes
precede
atrophy
neurodegeneration.
In
this
systematic
review,
we
provide
a
discussion
vivo
SV2A
PET
imaging
research
for
quantitative
assessment
various
dementia
conditions:
amnestic
Mild
Cognitive
Impairment
Alzheimer’s
disease,
Frontotemporal
dementia,
Progressive
supranuclear
palsy
Corticobasal
degeneration,
Parkinson’s
disease
Dementia
Lewy
bodies,
Huntington’s
Spinocerebellar
Ataxia.
We
discuss
main
findings
concerning
group
differences
clinical-cognitive
correlations,
explore
relations
between
other
markers
pathology.
Additionally,
touch
upon
healthy
ageing
outcomes
radiotracer
validation
studies.
Studies
were
identified
on
PubMed
Embase
2018
2023;
last
searched
3rd
July
2023.
total
36
studies
included,
comprising
5
normal
ageing,
21
clinical
studies,
10
Extracted
study
characteristics
participant
details,
methodological
aspects,
critical
findings.
summary,
small
but
growing
literature
has
revealed
different
spatial
patterns
among
neurodegenerative
disorders
correlate
cognitive
functioning,
supporting
potential
role
differential
diagnosis.
shows
tremendous
capability
novel
insights
into
aetiology
great
promise
as
biomarker
reduction.
Novel
directions
future
are
proposed,
including
(a)
longitudinal
larger
patient
cohorts
preclinical
dementias,
(b)
multi-modal
mapping
onto
processes,
(c)
monitoring
therapeutic
responses
assessing
drug
efficacy
trials.
Frontiers in Molecular Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Янв. 5, 2024
Amyotrophic
Lateral
Sclerosis
(ALS)
and
Frontotemporal
Dementia
(FTD)
are
debilitating
neurodegenerative
diseases
with
shared
pathological
features
like
transactive
response
DNA-binding
protein
of
43
kDa
(TDP-43)
inclusions
genetic
mutations.
Both
involve
synaptic
dysfunction,
contributing
to
their
clinical
features.
Synaptic
biomarkers,
representing
proteins
associated
function
or
structure,
offer
insights
into
disease
mechanisms,
progression,
treatment
responses.
These
biomarkers
can
detect
early,
track
its
evaluate
therapeutic
efficacy.
ALS
is
characterized
by
elevated
neurofilament
light
chain
(NfL)
levels
in
cerebrospinal
fluid
(CSF)
blood,
correlating
progression.
TDP-43
another
key
biomarker,
mislocalization
linked
dysfunction.
In
FTD,
tau
studied
as
biomarkers.
neuronal
pentraxins
(NPs),
including
pentraxin
2
(NPTX2),
receptor
(NPTXR),
FTD
pathology
cognitive
decline.
Advanced
technologies,
machine
learning
(ML)
artificial
intelligence
(AI),
aid
biomarker
discovery
drug
development.
Challenges
this
research
include
technological
limitations
detection,
variability
across
patients,
translating
findings
from
animal
models.
ML/AI
accelerate
analyzing
complex
data
predicting
outcomes.
early
personalized
strategies,
mechanisms.
While
challenges
persist,
advancements
interdisciplinary
efforts
promise
revolutionize
the
understanding
management
FTD.
This
review
will
explore
present
comprehension
discuss
significance
emphasize
prospects
obstacles.
Translational Psychiatry,
Год журнала:
2024,
Номер
14(1)
Опубликована: Март 14, 2024
Abstract
Late-life
depression
has
been
consistently
associated
with
lower
gray
matter
volume,
the
origin
of
which
remains
largely
unexplained.
Recent
in-vivo
PET
findings
in
early-onset
and
Alzheimer’s
Disease
suggest
that
synaptic
deficits
contribute
to
pathophysiology
these
disorders
may
therefore
volume
late-life
depression.
Here,
we
investigate
density
vivo
for
first
time
using
vesicle
glycoprotein
2A
receptor
radioligand
11
C-UCB-J.
We
included
24
currently
depressed
adults
(73.0
±
6.2
years,
16
female,
geriatric
scale
=
19.5
6.8)
36
age-
gender-matched
healthy
controls
(70.4
21
2.7
2.9)
underwent
simultaneous
C-UCB-J
positron
emission
tomography
(PET)
3D
T1-
T2-FLAIR
weighted
magnetic
resonance
(MR)
imaging
on
a
3-tesla
PET-MR
scanner.
used
analyses
variance
test
binding
volumes
differences
regions
implicated
The
group
showed
trend
hippocampus
(
p
0.04),
mesial
temporal
0.02)
prefrontal
cortex
compared
control
without
surviving
correction
multiple
comparison.
However,
no
were
found
nor
any
associations
between
depressive
symptoms.
Our
data
suggests
that,
contrast
Disease,
is
not
changes.
From
therapeutic
standpoint,
preserved
be
an
encouraging
finding.
Journal of Leukocyte Biology,
Год журнала:
2022,
Номер
112(5), С. 1297 - 1315
Опубликована: Сен. 23, 2022
Abstract
The
most
studied
HIV
eradication
approach
is
the
“shock
and
kill”
strategy,
which
aims
to
reactivate
latent
reservoir
by
latency
reversing
agents
(LRAs)
allowing
elimination
of
these
cells
immune-mediated
clearance
or
viral
cytopathic
effects.
CNS
an
anatomic
compartment
in
(persistent)
plays
important
role
HIV-associated
neurocognitive
disorder.
Restriction
blood–brain
barrier
for
maintenance
homeostasis
microenvironment,
includes
CNS-specific
cell
types,
expression
transcription
factors,
altered
immune
surveillance.
Within
predominantly
myeloid
such
as
microglia
perivascular
macrophages
are
thought
be
a
persistent
infection.
Nevertheless,
infection
T
astrocytes
might
also
impact
CNS.
Genetic
adaptation
this
microenvironment
results
genetically
distinct,
compartmentalized
populations
with
differences
profiles.
Because
profiles,
LRAs
have
different
effects
within
compared
periphery.
Moreover,
reactivation
brain
complex
could
detrimental
consequences.
Finally,
independent
activity
on
HIV,
themselves
can
adverse
neurologic
We
provide
extensive
overview
current
knowledge
strategy.
Subsequently,
we
reflect
promise
strategy
Abstract
Schizophrenia
is
a
chronic
disease
presented
with
psychotic
symptoms,
negative
impairment
in
the
reward
system,
and
widespread
neurocognitive
deterioration.
Disruption
of
synaptic
connections
neural
circuits
responsible
for
disease's
development
progression.
Because
deterioration
results
impaired
effective
processing
information.
Although
structural
impairments
synapse,
such
as
decrease
dendritic
spine
density,
have
been
shown
previous
studies,
functional
also
revealed
genetic
molecular
analysis
methods.
In
addition
to
abnormalities
protein
complexes
regulating
exocytosis
presynaptic
region
vesicle
release,
especially,
changes
proteins
related
postsynaptic
signaling
reported.
particular,
density
elements,
glutamate
receptors,
ion
channels
shown.
At
same
time,
effects
on
cellular
adhesion
structures
neurexin,
neuroligin,
cadherin
family
were
detected.
Of
course,
confusing
effect
antipsychotic
use
schizophrenia
research
should
be
considered.
antipsychotics
positive
synapses,
studies
indicate
independent
drug
use.
this
review,
synapse
structure
function
will
discussed.
