Frontiers in Aging Neuroscience,
Journal Year:
2023,
Volume and Issue:
15
Published: Aug. 15, 2023
Alzheimer’s
disease
(AD)
is
a
progressive
neurodegenerative
disorder
primarily
affecting
cognitive
functions.
However,
sensory
deficits
in
AD
start
to
draw
attention
due
their
high
prevalence
and
early
onsets
which
suggest
that
they
could
potentially
serve
as
diagnostic
biomarkers
even
contribute
the
progression.
This
literature
review
examines
cortical
pathological
changes
observed
visual,
auditory,
olfactory,
somatosensory
systems
patients,
well
various
animal
models.
Sensory
may
emerge
at
stages
of
AD,
or
precede
decline,
accompanied
by
including
amyloid-beta
deposition,
tauopathy,
gliosis,
alterations
neuronal
excitability,
synaptic
inputs,
functional
plasticity.
Notably,
these
are
more
pronounced
association
areas
superficial
layers,
explain
relative
preservation
basic
functions
but
display
higher
We
propose
impairment
progression
establish
cyclical
relationship
mutually
perpetuates
each
condition.
highlights
significance
with
without
emphasizes
need
for
further
research
develop
reliable
detection
intervention
through
systems.
Frontiers in Synaptic Neuroscience,
Journal Year:
2023,
Volume and Issue:
15
Published: March 9, 2023
The
synapse
has
consistently
been
considered
a
vulnerable
and
critical
target
within
Alzheimer’s
disease,
loss
is,
to
date,
one
of
the
main
biological
correlates
cognitive
decline
disease.
This
occurs
prior
neuronal
with
ample
evidence
that
synaptic
dysfunction
precedes
this,
in
support
idea
failure
is
crucial
stage
disease
pathogenesis.
two
pathological
hallmarks
abnormal
aggregates
amyloid
or
tau
proteins,
have
had
demonstrable
effects
on
physiology
animal
cellular
models
There
also
growing
these
proteins
may
synergistic
effect
neurophysiological
dysfunction.
Here,
we
review
some
findings
alterations
what
know
from
models.
First,
briefly
summarize
human
suggest
synapses
are
altered,
including
how
this
relates
network
activity.
Subsequently,
considered,
highlighting
mouse
pathology
role
play
dysfunction,
either
isolation
examining
pathologies
interact
specifically
focuses
function
observed
models,
typically
measured
using
electrophysiology
calcium
imaging.
Following
loss,
it
would
be
impossible
imagine
not
alter
oscillatory
activity
brain.
Therefore,
discusses
underpin
aberrant
patterns
seen
patients.
Finally,
an
overview
key
directions
considerations
field
covered.
includes
current
therapeutics
targeted
at
but
methods
modulate
rescue
patterns.
Other
important
future
avenues
note
include
non-neuronal
cell
types
such
as
astrocytes
microglia,
mechanisms
independent
will
certainly
continue
for
foreseeable
future.
Molecular Neurodegeneration,
Journal Year:
2023,
Volume and Issue:
18(1)
Published: July 20, 2023
Abstract
Human
studies
consistently
identify
bioenergetic
maladaptations
in
brains
upon
aging
and
neurodegenerative
disorders
of
(NDAs),
such
as
Alzheimer’s
disease,
Parkinson’s
Huntington’s
Amyotrophic
lateral
sclerosis.
Glucose
is
the
major
brain
fuel
glucose
hypometabolism
has
been
observed
regions
vulnerable
to
NDAs.
Many
susceptible
are
topological
central
hub
connectome,
linked
by
densely
interconnected
long-range
axons.
Axons,
key
components
have
high
metabolic
needs
support
neurotransmission
other
essential
activities.
Long-range
axons
particularly
injury,
neurotoxin
exposure,
protein
stress,
lysosomal
dysfunction,
etc.
Axonopathy
often
an
early
sign
neurodegeneration.
Recent
ascribe
axonal
maintenance
failures
local
dysregulation.
With
this
review,
we
aim
stimulate
research
exploring
metabolically
oriented
neuroprotection
strategies
enhance
or
normalize
bioenergetics
NDA
models.
Here
start
summarizing
evidence
from
human
patients
animal
models
reveal
correlation
between
connectomic
disintegration
aging/NDAs.
To
encourage
mechanistic
investigations
on
how
dysregulation
occurs
during
aging/NDAs,
first
review
current
literature
distinct
subdomains:
axon
initial
segments,
myelinated
arbors
harboring
pre-synaptic
boutons.
In
each
subdomain,
focus
organization,
activity-dependent
regulation
system,
external
glial
support.
Second,
mechanisms
regulating
nicotinamide
adenine
dinucleotide
(NAD
+
)
homeostasis,
molecule
for
energy
metabolism
processes,
including
NAD
biosynthetic,
recycling,
consuming
pathways.
Third,
highlight
innate
vulnerability
connectome
discuss
its
perturbation
As
deficits
developing
into
NDAs,
especially
asymptomatic
phase,
they
likely
exaggerated
further
impaired
energetic
cost
neural
network
hyperactivity,
pathology.
Future
interrogating
causal
relationship
vulnerability,
axonopathy,
amyloid/tau
pathology,
cognitive
decline
will
provide
fundamental
knowledge
therapeutic
interventions.
Brain,
Journal Year:
2024,
Volume and Issue:
147(5), P. 1726 - 1739
Published: March 11, 2024
Progressive
neuronal
loss
is
a
hallmark
feature
distinguishing
neurodegenerative
diseases
from
normal
ageing.
However,
the
underlying
mechanisms
remain
unknown.
Extracellular
K+
homeostasis
potential
mediator
of
injury
as
elevations
increase
excitatory
activity.
The
dysregulation
extracellular
and
potassium
channel
expressions
during
neurodegeneration
could
contribute
to
this
distinction.
Here
we
measured
cortical
concentration
([K+]e)
in
awake
wild-type
mice
well
murine
models
using
K+-sensitive
microelectrodes.
Unexpectedly,
aged
exhibited
significantly
lower
[K+]e
than
young
mice.
In
contrast,
was
consistently
elevated
Alzheimer's
disease
(APP/PS1),
amyotrophic
lateral
sclerosis
(ALS)
(SOD1G93A)
Huntington's
(R6/2)
models.
Cortical
resting
correlated
inversely
with
density
buffering
rate
but
positively
predicted
firing
rate.
Screening
astrocyte-selective
genomic
datasets
revealed
number
genes
that
were
downregulated
these
not
particular,
inwardly
rectifying
Kcnj10
ALS
ageing,
while
Fxyd1
Slc1a3,
each
which
acts
negative
regulator
uptake,
upregulated
by
astrocytes
both
Chronic
elevation
response
changes
gene
expression
attendant
hyperexcitability
may
drive
characteristic
diseases.
These
observations
suggest
be
due
aberrant
astrocytic
such,
highlight
fundamental
role
for
glial
dysfunction
neurodegeneration.
Nature Neuroscience,
Journal Year:
2024,
Volume and Issue:
27(10), P. 1880 - 1891
Published: Aug. 26, 2024
Abstract
Proteomics
can
shed
light
on
the
dynamic
and
multifaceted
alterations
in
neurodegenerative
disorders
like
Alzheimer’s
disease
(AD).
Combining
radioligands
measuring
β-amyloid
(Aβ)
plaques
tau
tangles
with
cerebrospinal
fluid
proteomics,
we
uncover
molecular
events
mirroring
different
stages
of
AD
pathology
living
humans.
We
found
127
differentially
abundant
proteins
(DAPs)
across
spectrum.
The
strongest
Aβ-related
were
mainly
expressed
glial
cells
included
SMOC1
ITGAM.
A
dozen
linked
to
ATP
metabolism
preferentially
neurons
independently
associated
tangle
load
accumulation.
Only
20%
DAPs
also
altered
other
diseases,
underscoring
AD’s
distinct
proteome.
Two
co-expression
modules
related,
respectively,
protein
microglial
immune
response
encompassed
most
DAPs,
opposing,
staggered
trajectories
along
continuum.
unveil
signatures
Aβ
proteinopathy
vivo,
offering
insights
into
complex
neural
responses
potential
biomarkers
therapeutics
targeting
stages.
Cells,
Journal Year:
2025,
Volume and Issue:
14(2), P. 143 - 143
Published: Jan. 19, 2025
Brain
plasticity
is
at
the
basis
of
many
cognitive
functions,
including
learning
and
memory.
It
includes
several
mechanisms
synaptic
extrasynaptic
changes,
neurogenesis,
formation
elimination
synapses.
The
transmission
involves
expression
immediate
early
genes
(IEGs)
that
regulate
neuronal
activity,
thereby
supporting
In
addition,
IEGs
are
involved
in
regulation
brain
cells’
metabolism,
proliferation,
survival,
establishment
multicellular
ensembles,
and,
presumably,
cell
competition
tissue.
this
review,
we
analyze
current
understanding
role
(c-Fos,
c-Myc,
Arg3.1/Arc)
controlling
physiological
pathological
conditions,
aging
neurodegeneration.
This
work
might
inspire
new
gene
therapy
strategies
targeting
to
plasticity,
potentially
prevent
or
mitigate
neurodegenerative
diseases.
Frontiers in Psychology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 18, 2025
This
perspective
article
addresses
the
potential
use
of
cortical
excitability
(CE)
as
an
indicator
cognitive
health
in
aging
people.
Changes
CE
may
be
considered
a
sign
resilience
to
decline
old
age.
The
authors
describe
research
on
and
its
link
function
older
adults
emphasize
that
it
is
promising,
non-invasive
measure
healthy
aging.
They
also
address
current
challenges
implementation,
need
for
standardized
measurement
protocols
possible
future
avenues
research.
If
properly
considered,
could
pave
way
early
detection
facilitate
targeted
interventions
promote
resilience.
Journal of Clinical Neurophysiology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 18, 2025
Purpose:
Patients
with
Alzheimer's
dementia
(AD)
who
do
not
have
a
history
of
epilepsy
higher
frequency
subclinical
epileptiform
discharge
(SED)
than
healthy
individuals.
This
meta-analysis
aims
to
investigate
the
SED
in
patients
AD
using
different
EEG
protocols
and
compare
rates
between
early-
late-onset
AD.
Methods:
study
adhered
Preferred
Reporting
Items
for
Systematic
Reviews
Meta-analysis
guidelines.
We
searched
various
databases
until
January
2024
studies
reporting
did
epilepsy.
A
was
conducted
random-effects
model.
Results:
Thirteen
involving
1,373
were
analyzed.
The
had
mean
age
71.2
years,
59.3%
women.
pooled
rate
found
be
18.3%.
extended
(26.7%)
routine
(12.1%).
It
also
observed
that
early-onset
(14.4%)
(43.9%)
those
(10.5
21.3%,
respectively).
Furthermore,
3.55
relative
risk
(
P
<
0.001)
compared
controls.
Specifically,
showed
significantly
developing
(relative
risk,
4.48;
0.001).
Conclusions:
Subclinical
high
AD,
particularly
early
onset
Biomedicines,
Journal Year:
2023,
Volume and Issue:
11(2), P. 355 - 355
Published: Jan. 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.
Neurobiology of Disease,
Journal Year:
2023,
Volume and Issue:
179, P. 106047 - 106047
Published: Feb. 23, 2023
Brain
functional
connectivity
in
dementia
has
been
assessed
with
dissimilar
EEG
metrics
and
estimation
procedures,
thereby
increasing
results'
heterogeneity.
In
this
scenario,
joint
analyses
integrating
information
from
different
may
allow
for
a
more
comprehensive
characterization
of
brain
interactions
subtypes.
To
test
hypothesis,
resting-state
electroencephalogram
(rsEEG)
was
recorded
individuals
Alzheimer's
Disease
(AD),
behavioral
variant
frontotemporal
(bvFTD),
healthy
controls
(HCs).
Whole-brain
estimated
the
source
space
using
101
types
connectivity,
capturing
linear
nonlinear
both
time
frequency-domains.
Multivariate
machine
learning
progressive
feature
elimination
run
to
discriminate
AD
HCs,
bvFTD
based
on
i)
frequency
bands,
ii)
complementary
frequency-domain
(e.g.,
instantaneous,
lagged,
total
connectivity),
iii)
time-domain
linearity
assumption
Pearson
correlation
coefficient
mutual
information).
<10%
all
possible
connections
were
responsible
differences
between
patients
controls,
atypical
never
captured
by
>1/4
measures.
Joint
revealed
patterns
hypoconnectivity
(patientsHCs)
groups
mainly
identified
regions.
These
atypicalities
differently
frequency-
metrics,
bandwidth-specific
fashion.
The
multi-metric
representation
whole-brain
evidenced
inadequacy
single-metric
approaches,
resulted
valid
alternative
selection
problem
connectivity.
reveal
interdependence
that
are
overlooked
single
contributing
reliable
interpretable
description
neurodegeneration.