Neuromodulators
affect
cognition
and
behavior
via
their
actions
on
brain
wide
neural
networks.
The
locus
coeruleus
norepinephrine
(LC-NE)
system
is
one
of
the
brain’s
major
neuromodulatory
systems.
Aging
neurological
diseases
lead
to
changes
in
structure
that
impact
normal
functioning
networks
Although
precise
nature
this
impact,
its
diagnosis
quantification
remain
a
challenge,
recent
studies
humans
animal
models
have
started
reveal
details
about
effects
intrinsic
neuromodulators
behavior.
These
findings
are
beginning
suggest
how
systems
neuroscience
approaches
might
help
develop
new
tests
supplement
range
established
clinical
assays
for
testing
cognitive
deficits
due
aging
Alzheimer’s
disease.
Here,
I
will
review
what
we
know
perform
computations
driving
perception
action
these
affected
by
activation
LC-NE
system.
examine
known
disease
related
resulting
action.
discuss
relationships
between
pupil
size,
recently
explored
with
precision
models.
how,
when
combined
perceptual
or
tests,
provide
basis
exploring
use
pupillometry
as
non-invasive
assay
age-
disease-related
decline
neuromodulatoryfunction.
Molecular Psychiatry,
Journal Year:
2024,
Volume and Issue:
29(7), P. 2001 - 2008
Published: Feb. 15, 2024
Abstract
The
locus
coeruleus-noradrenaline
system
regulates
brain-wide
neural
activity
involved
in
cognition
and
behavior.
Integrity
of
this
subcortical
neuromodulatory
is
proposed
to
be
a
substrate
cognitive
reserve
that
may
strengthened
by
lifetime
social
activity.
Conversely,
accumulation
tau
tangles
the
brainstem
coeruleus
nuclei
recently
studied
as
very
early
marker
Alzheimer’s
disease
(AD)
pathogenesis
vulnerability,
even
among
older
adults
without
impairment
or
significant
cerebral
AD
pathologies.
This
clinical-pathologic
study
examined
whether
tangle
density
was
cross-sectionally
associated
with
lower
antemortem
performance
142
cognitively
unimpaired
impaired
activity,
putative
factor,
mediated
association
cognition.
We
found
greater
for
whole
sample
group
alone
these
associations
were
independent
age,
sex,
education,
depressive
symptoms,
burden
amyloid
tau.
partially
level
These
findings
implicate
late-life
function
support
pathology
levels
pathologies,
specifically
who
are
unimpaired.
Early
impact
function,
turn,
influences
cognition,
prior
canonical
stages
AD.
Journal of Alzheimer s Disease,
Journal Year:
2024,
Volume and Issue:
99(1), P. 105 - 111
Published: April 12, 2024
Tau
accumulation
in
and
neurodegeneration
of
locus
coeruleus
(LC)
neurons
is
observed
Alzheimer's
disease
(AD).
We
investigated
whether
tangle
neuronal
density
the
rostral
caudal
LC
characterized
by
an
asymmetric
pattern
77
autopsy
cases
Rush
Memory
Aging
Project.
found
left-right
equivalence
for
across
individuals
with
without
AD
pathology.
However,
density,
particularly
caudal-rostral
axis
LC,
among
Asymmetry
may
signal
advanced
progression
should
be
considered
neuroimaging
studies
neurodegeneration.
Current Issues in Molecular Biology,
Journal Year:
2024,
Volume and Issue:
46(9), P. 10180 - 10199
Published: Sept. 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.
Neuromodulators
affect
cognition
and
behavior
via
their
actions
on
brain
wide
neural
networks.
The
locus
coeruleus
norepinephrine
(LC-NE)
system
is
one
of
the
brain’s
major
neuromodulatory
systems.
Aging
neurological
diseases
lead
to
changes
in
structure
that
impact
normal
functioning
networks
Although
precise
nature
this
impact,
its
diagnosis
quantification
remain
a
challenge,
recent
studies
humans
animal
models
have
started
reveal
details
about
effects
intrinsic
neuromodulators
behavior.
These
findings
are
beginning
suggest
how
systems
neuroscience
approaches
might
help
develop
new
tests
supplement
range
established
clinical
assays
for
testing
cognitive
deficits
due
aging
Alzheimer’s
disease.
Here,
I
will
review
what
we
know
perform
computations
driving
perception
action
these
affected
by
activation
LC-NE
system.
examine
known
disease
related
resulting
action.
discuss
relationships
between
pupil
size,
recently
explored
with
precision
models.
how,
when
combined
perceptual
or
tests,
provide
basis
exploring
use
pupillometry
as
non-invasive
assay
age-
disease-related
decline
neuromodulatoryfunction.
