Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
46(9), С. 10180 - 10199
Опубликована: Сен. 14, 2024
Neuromodulatory
subcortical
systems
(NSSs)
are
monoaminergic
and
cholinergic
neuronal
groups
that
markedly
precociously
involved
in
the
pathogenesis
of
many
neurodegenerative
disorders
(NDDs),
including
Parkinson’s
Alzheimer’s
diseases.
In
humans,
although
tools
have
been
developed
to
infer
information
on
these
nuclei,
encompassing
neuroimaging
neurophysiological
methods,
a
detailed
specific
direct
evaluation
their
cellular
features
vivo
has
difficult
obtain
until
recent
years.
The
development
induced
pluripotent
stem
cell
(iPSC)
models
allowed
research
deeply
delve
into
molecular
biology
NSS
neurons.
fact,
iPSCs
can
be
produced
easily
non-invasively
from
patients’
fibroblasts
or
circulating
blood
monocytes,
by
de-differentiating
those
cells
using
protocols,
then
re-differentiated
towards
neural
phenotypes,
which
may
reproduce
correspondent
brain
neurons
(including
ones)
same
patient.
this
review,
we
summarized
findings
obtained
field
NDDs
iPSCs,
with
aim
understand
how
reliably
might
represent
vitro
NSS.
We
found
most
current
literature
NSSs
focused
midbrain
dopaminergic
disease,
providing
interesting
results
pathophysiology
even
leading
first
human
autologous
transplantation.
Differentiation
protocols
for
noradrenergic,
cholinergic,
serotoninergic
also
recently
defined
published.
Thus,
it
expected
near
future,
approach
could
extend
other
NDDs.
Brain Structure and Function,
Год журнала:
2024,
Номер
229(5), С. 1317 - 1325
Опубликована: Апрель 16, 2024
Abstract
The
noradrenergic
nucleus
Locus
Coeruleus
(LC)
is
precociously
involved
in
Alzheimer’s
Disease
(AD)
pathology,
and
its
degeneration
progresses
during
the
course
of
disease.
Using
Magnetic
Resonance
Imaging
(MRI),
researchers
showed
also
vivo
patients
disruption
LC,
which
can
be
observed
both
Mild
Cognitively
Impaired
individuals
AD
demented
patients.
In
this
study,
we
report
results
a
follow-up
neuroradiological
assessment,
evaluated
LC
overtime
group
cognitively
impaired
patients,
submitted
to
MRI
at
baseline
end
2.5-year
follow-up.
We
found
that
progressive
vivo,
involving
entire
associated
with
clinical
diagnosis.
Our
findings
parallel
neuropathological
ones,
continuous
increase
neuronal
death
volumetric
atrophy
within
progression
Braak’s
stages
for
neurofibrillary
pathology.
This
supports
reliability
as
tool
exploring
integrity
central
system
neurodegenerative
disorders.
Journal of Clinical Medicine,
Год журнала:
2021,
Номер
10(8), С. 1555 - 1555
Опубликована: Апрель 7, 2021
Alzheimer’s
disease
(AD)
is
a
devastating
neurodegenerative
disorder
as
yet
without
effective
therapy.
Symptoms
of
this
typically
reflect
cortical
malfunction
with
local
neurohistopathology,
which
biased
investigators
to
search
for
focal
triggers
and
molecular
mechanisms.
Cortex,
however,
receives
massive
afferents
from
caudal
brain
structures,
do
not
only
convey
specific
information
but
powerfully
tune
ensemble
activity.
Moreover,
there
evidence
that
the
start
AD
subcortical.
The
brainstem
harbors
monoamine
systems,
establish
dense
innervation
in
both
allo-
neocortex.
Monoaminergic
synapses
can
co-release
neuropeptides
either
by
precisely
terminating
on
neurons
or,
when
being
“en
passant”,
instigate
volume
transmission.
Especially
due
its
early
damage,
ascending
monoaminergic
system
emerges
an
sign
possible
trigger
AD.
This
review
summarizes
involvement
cascaded
impairment
discusses
cellular
mechanisms
lead
their
dysfunction.
We
highlight
significance
therapeutic
challenges
transmitter
activating
system,
describe
role
changes
connections
distant
nuclei
AD,
summon
rapidly
increasing
diagnostic
window
during
last
few
years.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 26, 2024
Abstract
INTRODUCTION
The
Locus
Coeruleus
(LC)
is
linked
to
the
development
and
pathophysiology
of
neurodegenerative
diseases
such
as
Alzheimer’s
Disease
(AD).
Magnetic
Resonance
Imaging
based
LC
features
have
shown
potential
assess
integrity
in
vivo.
METHODS
We
present
a
Deep
Learning
segmentation
feature
extraction
method:
ELSI-Net
apply
it
healthy
aging
AD
dementia
datasets.
Agreement
expert
raters
previously
published
atlases
were
assessed.
aimed
reproduce
reported
differences
correlate
extracted
cerebrospinal
fluid
(CSF)
biomarkers
pathology.
RESULTS
demonstrated
high
agreement
atlases.
Previously
group
detected
correlations
CSF
found.
DISCUSSION
Although
we
found
excellent
performance,
further
evaluations
on
more
diverse
datasets
from
clinical
cohorts
are
required
for
conclusive
assessment
ELSI-Nets
general
applicability.
Highlights
thorough
evaluation
fully
automatic
method
termed
outperforms
previous
work
shows
with
manual
ratings
replicates
ELSI-Net’s
volume
correlates
pathology
RESEARCH
IN
CONTEXT
Systematic
Review:
authors
reviewed
literature
using
traditional
sources
(e.g.
Pubmed,
Google
Scholar).
there
several
publications
introducing
semi-automatic
methods
segmentation,
application
underexplored.
To
best
our
knowledge,
this
first
paper
approach
automated
dementia.
Interpretation:
Our
introduces
evaluates
an
improved
automatic,
analysis
approach.
results
suggest
very
practical
applicability,
e.g.
large-scale
studies
diseases.
Future
Directions:
can
be
used
large-
or
small-scale
ensure
robust
should
evaluated
larger,
comprising
varying
MRI
protocols
populations.
Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
46(9), С. 10180 - 10199
Опубликована: Сен. 14, 2024
Neuromodulatory
subcortical
systems
(NSSs)
are
monoaminergic
and
cholinergic
neuronal
groups
that
markedly
precociously
involved
in
the
pathogenesis
of
many
neurodegenerative
disorders
(NDDs),
including
Parkinson’s
Alzheimer’s
diseases.
In
humans,
although
tools
have
been
developed
to
infer
information
on
these
nuclei,
encompassing
neuroimaging
neurophysiological
methods,
a
detailed
specific
direct
evaluation
their
cellular
features
vivo
has
difficult
obtain
until
recent
years.
The
development
induced
pluripotent
stem
cell
(iPSC)
models
allowed
research
deeply
delve
into
molecular
biology
NSS
neurons.
fact,
iPSCs
can
be
produced
easily
non-invasively
from
patients’
fibroblasts
or
circulating
blood
monocytes,
by
de-differentiating
those
cells
using
protocols,
then
re-differentiated
towards
neural
phenotypes,
which
may
reproduce
correspondent
brain
neurons
(including
ones)
same
patient.
this
review,
we
summarized
findings
obtained
field
NDDs
iPSCs,
with
aim
understand
how
reliably
might
represent
vitro
NSS.
We
found
most
current
literature
NSSs
focused
midbrain
dopaminergic
disease,
providing
interesting
results
pathophysiology
even
leading
first
human
autologous
transplantation.
Differentiation
protocols
for
noradrenergic,
cholinergic,
serotoninergic
also
recently
defined
published.
Thus,
it
expected
near
future,
approach
could
extend
other
NDDs.
