Analysis of human brain RNA-seq data reveals combined effects of 4 types of RNA modifications and 18 types of programmed cell death on Alzheimer’s disease
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Апрель 3, 2025
Язык: Английский
CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease
Alzheimer s & Dementia,
Год журнала:
2024,
Номер
20(9), С. 6205 - 6220
Опубликована: Июль 6, 2024
Abstract
INTRODUCTION
We
aimed
to
unravel
the
underlying
pathophysiology
of
neurodegeneration
(N)
markers
neurogranin
(Ng),
neurofilament
light
(NfL),
and
hippocampal
volume
(HCV),
in
Alzheimer's
disease
(AD)
using
cerebrospinal
fluid
(CSF)
proteomics.
METHODS
Individuals
without
dementia
were
classified
as
A+
(CSF
amyloid
beta
[Aβ]42),
T+
phosphorylated
tau181),
N+
or
N−
based
on
Ng,
NfL,
HCV
separately.
CSF
proteomics
generated
compared
between
groups
analysis
covariance.
RESULTS
Only
a
few
individuals
A+T+Ng−.
A+T+Ng+
A+T+NfL+
showed
different
proteomic
profiles
A+T+Ng−
A+T+NfL−,
respectively.
Both
Ng+
NfL+
associated
with
neuroplasticity,
though
opposite
directions.
Compared
A+T+HCV−,
A+T+HCV+
changes,
oxidative
stress.
DISCUSSION
Different
N
are
distinct
neurodegenerative
processes
should
not
be
equated.
may
differentially
complement
staging
beyond
tau.
Our
findings
suggest
that
Ng
an
optimal
marker,
given
its
low
incongruency
tau
pathophysiology.
Highlights
In
disease,
(Ng)+,
(NfL)+,
(HCV)+
differential
protein
expression
fluid.
although
HCV+
related
Neurodegeneration
refine
might
it
relates
more
closely
Язык: Английский
Clarifying the association of CSF Aβ, tau, BACE1, and neurogranin with AT(N) stages in Alzheimer disease
Molecular Neurodegeneration,
Год журнала:
2024,
Номер
19(1)
Опубликована: Окт. 8, 2024
Abstract
Background
Current
AT(N)
stratification
for
Alzheimer’s
disease
(AD)
accounts
complex
combinations
of
amyloid
(A),
tau
proteinopathy
(T)
and
neurodegeneration
(N)
signatures.
Understanding
the
transition
between
these
different
stages
is
a
major
challenge,
especially
in
view
recent
development
modifying
therapy.
Methods
This
an
observational
study,
CSF
levels
Tau,
pTau181,
pTau217,
Aβ38/40/42,
sAPPα/β,
BACE1
neurogranin
were
measured
BALTAZAR
cohort
cognitively
impaired
patients
Alzheimer's
Disease
Neuroimaging
Initiative
(ADNI).
Biomarkers
related
to
framework.
(A)
defined
with
Aβ42/40
ratio
pTau217
respectively,
ADNI
PET.
was
using
total
both
cohorts.
Results
As
expected,
Aβ42
decreased
progressively
AD
continuum
going
from
A-T-N-
A
+
T
N
profile.
On
other
hand,
Tau
pTau181
increased
disease.
The
final
N-
led
sharp
increase
Aβ38,
sAPP
levels.
Synaptic
biomarkers
neurogranin,
lowest
initial
T-N-
stage
.
closely
Conclusions
early
phenotype
(A
T-N-)
primarily
impacts
synaptic
function.
appearance
then
associated
significant
progressive
pathological
biomarkers.
Our
main
finding
that
indicator
rather
than
,
elevated
protein
beta-amyloid
peptides.
may
potentially
fuel
cascade
positive
feedback
loop.
Overall,
our
data
provide
further
insights
into
understanding
interconnected
processes
amyloid,
tau,
underlying
Язык: Английский