bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 3, 2025
Early-stage
Alzheimer's
pathology
correlates
with
disrupted
neuronal
excitability,
which
can
drive
network
and
cognitive
dysfunction
even
prior
to
neurodegeneration.
However,
the
emergence
extent
of
these
changes
may
vary
by
brain
region
cell
types
situated
in
those
regions.
Here
we
aimed
investigate
effects
AD
on
different
neuron
subtypes
both
entorhinal
cortex,
a
enhanced
early
AD,
primary
visual
relatively
unaffected
early-stage
AD.
We
designed
employed
semi-automated
patch
clamp
electrophysiology
apparatus
record
from
fast-spiking
parvalbumin
interneurons
excitatory
neurons
regions,
recording
over
150
cells
young
adult
APP-KI
mice.
In
amyloid
overproduction
resulted
PV
interneuron
hypoexcitability,
whereas
were
concurrently
hyperexcitable.
Conversely,
either
subclass
largely
cortex.
Together,
findings
suggest
that
but
not
play
an
integral
role
progression.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(5), P. 2361 - 2361
Published: March 6, 2025
Alzheimer’s
disease
(AD)
is
a
complex,
genetically
heterogeneous
disorder.
The
diverse
phenotypes
associated
with
AD
result
from
interactions
between
genetic
and
environmental
factors,
influencing
multiple
biological
pathways
throughout
progression.
Network-based
approaches
offer
way
to
assess
phenotype-specific
states.
In
this
study,
we
calculated
key
network
metrics
characterize
the
transcriptional
structure
organization
in
LOAD,
focusing
on
genes
implicated
pathology
within
dorsolateral
prefrontal
cortex
(DLPFC).
Our
findings
revealed
disease-specific
coexpression
markers
metabolic
functions.
Additionally,
significant
differences
were
observed
at
both
mesoscopic
local
levels
control
networks,
along
restructuring
of
gene
functions
into
distinct
modules.
These
results
show
molecular
reorganization
program
occurring
highlighting
specific
adaptations
that
may
contribute
or
cellular
responses
pathological
stressors.
support
development
unified
model
for
causal
mechanisms
AD,
suggesting
its
manifestations
arise
working
together
produce
disease’s
complex
clinical
patho-phenotype.
Alzheimer s & Dementia,
Journal Year:
2025,
Volume and Issue:
21(3)
Published: March 1, 2025
We
systematically
reviewed
and
meta-analyzed
bulk
RNA
sequencing
(RNAseq)
studies
comparing
Alzheimer's
disease
(AD)
patients
to
controls
in
human
brain
tissue.
searched
PubMed,
Web
of
Science,
Scopus
for
RNAseq
studies,
excluding
re-analyses
limited
small
RNAs
or
gene
panels.
developed
10
criteria
quality
assessment
performed
a
meta-analysis
on
three
high-quality
datasets.
Of
3266
records,
24
qualified
the
systematic
review,
one
study
with
datasets
meta-analysis.
The
identified
571
differentially
expressed
genes
(DEGs)
temporal
lobe
189
frontal
lobe,
including
CLU
GFAP.
Pathway
analysis
suggested
reactivation
developmental
processes
adult
AD
brain.
Limited
data
availability
constrained
These
findings
underscore
need
rigorous
methods
transcriptomic
research
better
identify
changes
advance
biomarker
therapeutic
development.
This
review
is
registered
PROSPERO
(CRD42023466522).
Comprehensive
review:
Conducted
first
non-demented
using
primary
Identified
AD,
revealing
potential
targets.
discovery:
Highlighted
key
overlapping
pathways
such
as
"tube
morphogenesis"
"neuroactive
ligand-receptor
interaction"
that
may
play
critical
roles
AD.
Emphasized
importance
methodological
rigor
tools
guide
future
Acknowledged
access
complete
tables
lack
diversity
existing
datasets,
which
some
analysis.
Research Square (Research Square),
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 17, 2025
The
biological
mechanisms
underlying
the
increased
prevalence
of
Alzheimer's
disease
(AD)
in
women
remain
undefined.
While
previous
case/control
studies
have
identified
sex-biased
molecular
pathways,
sex-specific
relationships
between
gene
expression
and
AD
endophenotypes,
particularly
involving
sex
chromosomes,
are
underexplored.
With
bulk
transcriptomic
data
across
3
brain
regions
from
767
decedents,
we
investigated
associations
post-mortem
β-amyloid
tau,
as
well
antemortem
longitudinal
cognition.
Among
23,118
significant
associations,
10%
were
sex-specific,
with
73%
these
females
primarily
associated
tau
tangles
cognition
(90%).
Notably,
four
X-linked
genes,
MCF2
,
HDAC8
FTX
SLC10A3
demonstrated
differences
their
endophenotypes
(i.e.,
x
interaction).
Our
results
also
uncovered
including
a
female-specific
role
neuroinflammation
neuronal
development,
underscoring
importance
sex-aware
analyses
to
advance
precision
medicine
approaches
AD.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 3, 2025
Early-stage
Alzheimer's
pathology
correlates
with
disrupted
neuronal
excitability,
which
can
drive
network
and
cognitive
dysfunction
even
prior
to
neurodegeneration.
However,
the
emergence
extent
of
these
changes
may
vary
by
brain
region
cell
types
situated
in
those
regions.
Here
we
aimed
investigate
effects
AD
on
different
neuron
subtypes
both
entorhinal
cortex,
a
enhanced
early
AD,
primary
visual
relatively
unaffected
early-stage
AD.
We
designed
employed
semi-automated
patch
clamp
electrophysiology
apparatus
record
from
fast-spiking
parvalbumin
interneurons
excitatory
neurons
regions,
recording
over
150
cells
young
adult
APP-KI
mice.
In
amyloid
overproduction
resulted
PV
interneuron
hypoexcitability,
whereas
were
concurrently
hyperexcitable.
Conversely,
either
subclass
largely
cortex.
Together,
findings
suggest
that
but
not
play
an
integral
role
progression.
