Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Dec. 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
Frontiers in Aging Neuroscience,
Journal Year:
2024,
Volume and Issue:
16
Published: April 18, 2024
This
manuscript
presents
a
thorough
review
of
synaptic
vesicle
glycoprotein
2A
(SV2A)
as
biomarker
for
integrity
using
Positron
Emission
Tomography
(PET)
in
neurodegenerative
diseases.
Synaptic
pathology,
characterized
by
loss,
has
been
linked
to
various
brain
Therefore,
there
is
need
minimally
invasive
approach
measuring
density
living
human
patients.
Several
radiotracers
targeting
protein
have
created
and
effectively
adapted
use
subjects
through
PET
scans.
SV2A
an
integral
found
the
membranes
vesicles
all
terminals
widely
distributed
throughout
brain.
The
delves
into
development
SV2A-specific
radiotracers,
highlighting
their
advancements
limitations
Among
these
tracers,
11C-UCB-J
most
used
so
far.
We
summarize
discuss
increasing
body
research
that
compares
measurements
with
other
established
indicators
diseases,
including
cognitive
performance
radiological
findings,
thus
providing
comprehensive
analysis
SV2A's
effectiveness
reliability
diagnostic
tool
contrast
traditional
markers.
Although
literature
overall
suggests
promise
therapeutic
monitoring
tool,
uncertainties
persist
regarding
superiority
compared
available
also
underscores
paucity
studies
characterizing
distribution
loss
tissue
from
patients
emphasizing
generate
quantitative
neuropathological
maps
cases
diseases
fully
harness
potential
imaging
clinical
settings.
conclude
outlining
future
directions,
stressing
importance
integrating
biomarkers
assessments
longitudinal
track
changes
disease
progression,
which
could
lead
breakthroughs
early
diagnosis
evaluation
new
treatments.
Brain Imaging and Behavior,
Journal Year:
2024,
Volume and Issue:
18(5), P. 1001 - 1009
Published: May 24, 2024
Abstract
The
insula,
a
crucial
hub
of
the
human
brain
network,
can
be
divided
into
anterior
and
posterior
regions.
Previous
studies
have
reported
that
different
insula
subregions
play
various
roles
in
amnestic
mild
cognitive
impairment
(aMCI).
However,
longitudinal
changes
functional
connectivity
(FC)
each
subregion
aMCI
patients
over
time
remain
unclear.
Twenty
20
healthy
controls
(HCs)
were
recruited
underwent
resting-state
magnetic
resonance
imaging
(fMRI)
scans
neuropsychological
assessments
at
baseline
15-month
follow-up.
FMRI
data
preprocessed
using
SPM
12
CONN
toolbox.
Two-way
analysis
covariance
was
used
to
compare
FC
with
covariates
including
sex,
age,
education,
follow-up
interval,
volume
gray
matter,
global
correlation
(GCOR).
Pearson’s
evaluate
relationship
between
subregional
performance
patients.
In
patients,
right
exhibited
significantly
increased
left
cingulate
cortex,
whereas
decreased
precuneus
compared
HCs.
Furthermore,
cortex
correlated
cognition
current
findings
revealed
alterations
provided
new
insights
neurodegenerative
process
Human Brain Mapping,
Journal Year:
2023,
Volume and Issue:
44(11), P. 4239 - 4255
Published: June 3, 2023
Abstract
There
is
a
pressing
need
to
understand
the
factors
that
predict
prognosis
in
progressive
supranuclear
palsy
(PSP)
and
corticobasal
syndrome
(CBS),
with
high
heterogeneity
over
poor
average
survival.
We
test
hypothesis
magnitude
distribution
of
connectivity
changes
PSP
CBS
rate
progression
survival
time,
using
datasets
from
Cambridge
Centre
for
Parkinson‐plus
UK
National
Research
Network
(PROSPECT‐MR).
Resting‐state
functional
MRI
images
were
available
146
participants
PSP,
82
CBS,
90
healthy
controls.
Large‐scale
networks
identified
through
independent
component
analyses,
correlations
taken
between
time
series.
Independent
analysis
was
also
used
select
between‐network
components
compare
baseline
clinical
severity,
longitudinal
change
Transdiagnostic
predictors
partial
least
squares
regression
Cox
models,
compared
patients'
demographics,
structural
imaging,
scores
five‐fold
cross‐validation.
In
differed
controls,
associated
disease
related
severity.
A
transdiagnostic
predicted
beyond
demographic
motion
metrics
but
lower
accuracy
than
an
optimal
model
included
imaging
measures.
Cortical
atrophy
enhanced
most
predictive
Between‐network
variability
does
not
improve
metrics.
Neuropsychopharmacology,
Journal Year:
2024,
Volume and Issue:
50(1), P. 164 - 183
Published: Aug. 12, 2024
Abstract
Synapses
are
implicated
in
many
neuropsychiatric
illnesses.
Here,
we
provide
an
overview
of
vivo
techniques
to
index
synaptic
markers
patients.
Several
positron
emission
tomography
(PET)
tracers
for
vesicle
glycoprotein
2
A
(SV2A)
show
good
reliability
and
selectivity.
We
review
over
50
clinical
studies
including
1700
participants,
compare
findings
healthy
ageing
across
disorders,
addiction,
schizophrenia,
depression,
posttraumatic
stress
disorder,
neurodegenerative
tauopathies,
Huntington’s
disease
α-synucleinopathies.
These
lower
SV2A
measures
cortical
brain
regions
most
these
disorders
relative
volunteers,
with
the
well-replicated
whilst
changes
chorea,
Parkinson’s
disease,
corticobasal
degeneration
progressive
supranuclear
palsy
predominantly
subcortical.
PET
correlated
functional
connectivity
networks,
a
number
other
function,
glucose
metabolism.
However,
majority
found
no
relationship
between
grey
matter
volume
measured
magnetic
resonance
imaging
measures.
Cognitive
dysfunction,
domains
working
memory
executive
replicated
inverse
relationships
diagnoses,
initial
also
suggest
transdiagnostic
mood
anxiety
symptoms.
This
suggests
that
abnormalities
could
be
common
pathophysiological
substrate
underlying
cognitive
and,
potentially,
affective
consider
limitations
evidence
future
directions;
highlighting
need
develop
postsynaptic
longitudinal
test
causal
mechanisms.
Molecular Psychiatry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 18, 2024
Amyloid
accumulation
in
Alzheimer's
disease
(AD)
is
associated
with
synaptic
damage
and
altered
connectivity
brain
networks.
While
measures
of
amyloid
biochemical
changes
mouse
models
have
utility
for
translational
studies
certain
therapeutics,
preclinical
analysis
using
clinically
relevant
fMRI
has
not
been
well
developed
agents
intended
to
improve
neural
Here,
we
conduct
a
longitudinal
study
double
knock-in
model
AD
(AppNL-G-F/hMapt),
monitoring
by
means
resting-state
fMRI.
the
4-month-old
mice
are
indistinguishable
from
wild-type
controls
(WT),
decreased
default-mode
network
significant
relative
WT
6
months
age
pronounced
9
age.
In
second
cohort
20-month-old
persistent
functional
deficits
WT,
assess
impact
two-months
oral
treatment
silent
allosteric
modulator
mGluR5
(BMS-984923/ALX001)
known
rescue
density.
Functional
aged
reversed
mGluR5-directed
treatment.
The
application
enabled
us
define
time
trajectory
AD-related
connectivity,
demonstrate
translatable
metric
emergence,
progression,
response
synapse-rescuing
