Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases
Genes,
Год журнала:
2025,
Номер
16(2), С. 135 - 135
Опубликована: Янв. 24, 2025
Neurodegenerative
diseases,
such
as
Alzheimer’s
disease
(AD),
Parkinson’s
(PD),
Huntington’s
(HD),
and
amyotrophic
lateral
sclerosis
(ALS),
represent
a
growing
societal
challenge
due
to
their
irreversible
progression
significant
impact
on
patients,
caregivers,
healthcare
systems.
Despite
advances
in
clinical
imaging-based
diagnostics,
these
diseases
are
often
detected
at
advanced
stages,
limiting
the
effectiveness
of
therapeutic
interventions.
Recent
breakthroughs
genomic
transcriptomic
technologies,
including
whole-genome
sequencing,
single-cell
RNA
sequencing
(scRNA-seq),
CRISPR-based
screens,
have
revolutionized
field,
offering
new
avenues
for
early
diagnosis
personalized
prognosis.
Genomic
approaches
elucidated
disease-specific
genetic
risk
factors
molecular
pathways,
while
studies
identified
stage-specific
biomarkers
that
correlate
with
severity.
Furthermore,
genome-wide
association
(GWAS),
polygenic
scores
(PRS),
spatial
transcriptomics
enabling
stratification
patients
based
profiles
prognostic
trajectories.
Advances
functional
genomics
uncovered
actionable
targets,
ATXN2
ALS
TREM2
AD,
paving
way
tailored
strategies.
achievements,
challenges
remain
translating
discoveries
into
practice
heterogeneity
complexity
neurodegenerative
pathophysiology.
Future
integration
technologies
holds
promise
transforming
diagnostic
paradigms,
hope
improved
patient
outcomes
precision
medicine
approaches.
Язык: Английский
Integrating amyloid and tau imaging with proteomics and genomics in Alzheimer’s disease
Cell Reports Medicine,
Год журнала:
2024,
Номер
5(9), С. 101735 - 101735
Опубликована: Сен. 1, 2024
Язык: Английский
Lipid nanoparticle (LNP) mediated mRNA delivery in neurodegenerative diseases
Journal of Controlled Release,
Год журнала:
2025,
Номер
unknown, С. 113641 - 113641
Опубликована: Март 1, 2025
Язык: Английский
Synaptic vulnerability to amyloid-β and tau pathologies differentially disrupts emotional and memory neural circuits
Molecular Psychiatry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
Alzheimer's
disease
(AD)
is
characterized
by
memory
loss
and
neuropsychiatric
symptoms
associated
with
cerebral
amyloid-β
(Aβ)
tau
pathologies,
but
whether
how
these
factors
differentially
disrupt
neural
circuits
remains
unclear.
Here,
we
investigated
the
vulnerability
of
emotional
to
Aβ
pathologies
in
mice
expressing
mutant
human
amyloid
precursor
protein
(APP),
Tau
or
both
APP/Tau
excitatory
neurons.
develop
age-
sex-dependent
phosphorylated
latter
exacerbated
at
early
stages,
vulnerable
brain
regions.
Early
deficits
were
hippocampal
pathology
mice,
whereas
anxiety
fear
appeared
linked
intracellular
basolateral
amygdala
(BLA)
APP
mice.
Transcriptome
profiling
revealed
gene
changes
affecting
myelination
RNA
processing
inflammation
synaptic-related
pathways
6
months.
At
9
months,
detected
common
region-specific
astrocytic,
microglia
63
AD-associated
genes
hippocampus
BLA
Spatial
learning
synaptic
accumulation
synapse
disruption
disturbances
not
BLA.
Interestingly,
exhibited
synergistic
detrimental
effects
long-term
potentiation
(LTP)
they
counteract
each
other
mitigate
LTP
impairments
amygdala.
These
findings
indicate
that
cause
synergize
induce
dysfunction
immune
responses,
contributing
differing
AD.
Язык: Английский
Integration of Single-Cell and Spatial Transcriptomic Data Reveals Spatial Architecture and Potential Biomarkers in Alzheimer’s Disease
Molecular Neurobiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 15, 2024
Язык: Английский
Functional network disruption in cognitively unimpaired autosomal dominant Alzheimer’s disease: a magnetoencephalography study
Brain Communications,
Год журнала:
2024,
Номер
6(6)
Опубликована: Янв. 1, 2024
Abstract
Understanding
the
nature
and
onset
of
neurophysiological
changes,
selective
vulnerability
central
hub
regions
in
functional
network,
may
aid
managing
growing
impact
Alzheimer’s
disease
on
society.
However,
precise
alterations
occurring
pre-clinical
stage
human
remain
controversial.
This
study
aims
to
provide
increased
insights
quantitative
during
a
true
early
disease.
Using
high
spatial
resolution
source-reconstructed
magnetoencephalography,
we
investigated
regional
whole-brain
changes
unique
cohort
11
cognitively
unimpaired
individuals
with
pathogenic
mutations
presenilin-1
or
amyloid
precursor
protein
gene
1:3
matched
control
group
(n
=
33)
median
age
49
years.
We
examined
several
magnetoencephalography
measures
that
have
been
shown
robust
detecting
differences
sporadic
patients
are
sensitive
excitation-inhibition
imbalance.
includes
spectral
power
connectivity
different
frequency
bands.
also
using
disruption
index.
To
understand
how
change
as
progresses
through
its
stage,
correlations
between
outcomes
various
clinical
variables
like
were
analysed.
A
comparison
mutation
carriers
controls
revealed
oscillatory
slowing,
characterized
by
widespread
higher
theta
(4–8
Hz)
power,
lower
posterior
peak
occipital
alpha
2
(10–13
power.
Functional
analyses
presented
(amplitude-based)
(8–13
beta
(13–30
bands,
predominantly
located
parieto-temporal
regions.
Furthermore,
found
significant
index
for
(phase-based)
band,
attributed
both
‘non-hub’
alongside
disruption.
Neurophysiological
did
not
correlate
indicators
progression
after
multiple
comparisons
correction.
Our
findings
evidence
slowing
occur
before
cognitive
impairment
autosomal
dominant
leading
The
direction
these
comparable
those
observed
stages
disease,
suggest
an
imbalance,
fit
activity-dependent
degeneration
hypothesis.
These
prove
useful
diagnosis
intervention
future.
Язык: Английский
Regional vulnerability to Aβ and tau pathology
Nature Reviews Neurology,
Год журнала:
2024,
Номер
20(3), С. 133 - 133
Опубликована: Фев. 7, 2024
Язык: Английский
How Alzheimer's Abeta propagates and triggers tau pathology in intact neurons
Tomoya Sasahara,
Hongo Shoko,
Mika Ito
и другие.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 29, 2024
Abstract
Alzheimer’s
disease
begins
with
Aβ
accumulation,
progresses
to
tau
aggregates
and
results
in
widespread
neurodegeneration
1-3
.
Simultaneous
propagation
of
from
very
limited
wide
distant
brain
regions
is
one
the
outstanding
events
early
stage.
Here,
we
demonstrate
that
neurovascular
unit
4,5
comprising
capillaries
pericytes,
machinery
supplying
oxygen
glucose
neurons,
also
for
propagating
effector
molecules
impose
pathologies
on
intact
neurons.
We
discovered
two
distinct
signaling
cascades,
activated
capillary
endothelial
cells
other
pericytes.
At
origin
either
cascade,
identified
amylospheroid
(ASPD)
6,7
,
a
highly
toxic
30-mer
assembly
Aβ,
its
sole
target
NKAα3
8
neuron-specific
isoform
Na
+
,K
-ATPase
9,10
but
present
In
cells,
ASPD
binding
releases
angiotensin
II,
which
increases
β-secretase
causing
huge
increase
42
resultant
accumulation.
an
unknown
molecule
activates
δ-secretase
further
augmenting
producing
pathogenic
1-368
fragment.
Thus,
are
directly
linked.
Stopping
cascades
near
by
inhibiting
ASPD-NKAα3
interaction
may
provide
new
therapeutic
approach.
Язык: Английский
Local molecular and connectomic contributions of tau-related neurodegeneration
GeroScience,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 30, 2024
Язык: Английский
Morphometric Similarity Patterning of Amyloid-β and Tau Proteins Correlates with Transcriptomics in the Alzheimer’s Disease Continuum
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(23), С. 12871 - 12871
Опубликована: Ноя. 29, 2024
Bridging
the
gap
between
cortical
morphometric
remodeling
and
gene
expression
can
help
to
clarify
effects
of
selective
brain
accumulation
Amyloid-β
(Aβ)
tau
proteins
occurring
in
Alzheimer's
disease
(AD).
To
this
aim,
we
derived
similarity
(MS)
networks
from
126
Aβ-
tau-positive
(Aβ+/tau+)
172
Aβ-/tau-
subjects,
investigated
association
group-wise
regional
MS
differences
transcriptional
correlates
thanks
an
imaging
transcriptomics
approach
grounded
Allen
Human
Brain
Atlas
(AHBA).
The
expressed
with
highest
correlation
alterations
was
Язык: Английский