Alzheimer s Research & Therapy,
Год журнала:
2025,
Номер
17(1)
Опубликована: Фев. 13, 2025
Early
diagnosis
and
accurate
prognosis
of
cognitive
decline
in
Alzheimer's
disease
(AD)
is
important
to
timely
assignment
optimal
treatment
modes.
We
aimed
develop
a
deep
learning
model
predict
conversion
guide
re-assignment
decisions
more
intensive
therapies
where
needed.
Longitudinal
data
including
five
variable
sets,
i.e.
demographics,
medical
history,
neuropsychological
outcomes,
laboratory
neuroimaging
results,
from
the
Disease
Neuroimaging
Initiative
(ADNI)
cohort
were
analyzed.
first
developed
predicted
using
all
sets.
then
gradually
removed
sets
obtained
parsimonious
models
for
four
different
years
forecasting
after
baseline
within
acceptable
frames
reduction
overall
fit
(AUC
remaining
>
0.8).
A
total
607
individuals
included
at
baseline,
whom
538
participants
followed
up
12
months,
482
24
268
36
months
280
48
months.
Predictive
performance
was
excellent
with
AUCs
ranging
0.87
0.92
when
considered.
Parsimonious
prediction
that
still
had
good
AUC
0.80-0.84
established,
each
only
two
Neuropsychological
outcomes
models.
In
addition,
biomarker
year
1
2,
imaging
3
demographics
4.
Under
our
pre-set
threshold,
rate
upgrade
according
always
higher
than
actual
so
as
decrease
false
positive
rate,
indicating
proportion
patients
who
would
have
missed
upgraded
based
on
prognostic
although
they
actually
needed
it.
Neurophysiological
tests
combined
other
indicator
vary
along
AD
continuum
can
improve
provide
aid
clinical
leading
improved
management
disease.
ClinicalTrials.gov
Identifier:
NCT00106899
(Registration
Date:
31
March
2005).
New England Journal of Medicine,
Год журнала:
2024,
Номер
390(8), С. 712 - 722
Опубликована: Фев. 21, 2024
Biomarker
changes
that
occur
in
the
period
between
normal
cognition
and
diagnosis
of
sporadic
Alzheimer's
disease
have
not
been
extensively
investigated
longitudinal
studies.
Chemical Reviews,
Год журнала:
2024,
Номер
124(20), С. 11242 - 11347
Опубликована: Окт. 9, 2024
Biopsy,
including
tissue
and
liquid
biopsy,
offers
comprehensive
real-time
physiological
pathological
information
for
disease
detection,
diagnosis,
monitoring.
Fluorescent
probes
are
frequently
selected
to
obtain
adequate
on
processes
in
a
rapid
minimally
invasive
manner
based
their
advantages
biopsy.
However,
conventional
fluorescent
have
been
found
show
aggregation-caused
quenching
(ACQ)
properties,
impeding
greater
progresses
this
area.
Since
the
discovery
of
aggregation-induced
emission
luminogen
(AIEgen)
promoted
advancements
molecular
bionanomaterials
owing
unique
high
quantum
yield
(QY)
signal-to-noise
ratio
(SNR),
Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring,
Год журнала:
2025,
Номер
17(1)
Опубликована: Янв. 1, 2025
Abstract
INTRODUCTION
Blood‐based
biomarkers
seem
promising
for
the
diagnosis
of
Alzheimer's
disease
(AD).
METHODS
We
performed
a
systematic
review
and
meta‐analysis
on
potential
blood
phosphorylated
Tau181
(p‐tau181)
to
differentiate
amyloid‐positive
(A+)
amyloid‐negative
(A−)
subjects.
Two
meta‐analyses
were
conducted,
showing
mean
p‐tau
values
in
cerebrospinal
fluid
(CSF)
A+
A−
group,
second
comparing
concentrations
CSF
among
versus
A‐
participants,
by
laboratory
assessment
method.
RESULTS
Eighteen
studies
(2764
5646
subjects)
included.
The
single‐group
showed
higher
p‐tau181
than
group.
In
head‐to‐head
meta‐analysis,
reliably
differentiated
patients
from
participants.
DISCUSSION
Regardless
technique,
differentiates
Therefore,
it
might
have
important
applications
early
inclusion
clinical
trials
AD
patients.
Highlights
role
blood‐based
discriminating
is
still
uncertain.
Blood
distinguishes
allow
trials.
Alzheimer s & Dementia,
Год журнала:
2023,
Номер
19(12), С. 5872 - 5884
Опубликована: Июль 26, 2023
Abstract
INTRODUCTION
The
use
of
applied
modeling
in
dementia
risk
prediction,
diagnosis,
and
prognostics
will
have
substantial
public
health
benefits,
particularly
as
“deep
phenotyping”
cohorts
with
multi‐omics
data
become
available.
METHODS
This
narrative
review
synthesizes
understanding
models
digital
technologies,
terms
diagnostic
discrimination,
prognosis,
progression.
Machine
learning
approaches
show
evidence
improved
predictive
power
compared
to
standard
clinical
scores
predicting
dementia,
the
potential
decompose
large
numbers
variables
into
relatively
few
critical
predictors.
RESULTS
focuses
on
key
areas
emerging
promise
including:
emphasis
easier,
more
transparent
sharing
cohort
access;
integration
high‐throughput
biomarker
electronic
record
modeling;
progressing
beyond
primary
prediction
secondary
outcomes,
for
example,
treatment
response
physical
health.
DISCUSSION
Such
benefit
also
from
improvements
remote
measurement,
whether
cognitive
(e.g.,
online),
or
naturalistic
watch‐based
accelerometry).
Frontiers in Aging Neuroscience,
Год журнала:
2023,
Номер
15
Опубликована: Июнь 2, 2023
The
most
prevalent
genetic
risk
factor
for
Alzheimer’s
disease
(AD)
is
Apolipoprotein
E
(ApoE),
a
gene
located
on
chromosome
19
that
encodes
three
alleles
(e2,
e3,
and
e4)
give
rise
to
the
ApoE
subtypes
E2,
E3,
E4,
respectively.
E2
E4
have
been
linked
increased
plasma
triglyceride
concentrations
are
known
play
critical
role
in
lipoprotein
metabolism.
prominent
pathological
features
of
AD
mainly
include
senile
plaques
formed
by
amyloid
β
(Aβ
42
)
aggregation
neuronal
fibrous
tangles
(NFTs),
deposited
composed
Aβ
hyperphosphorylation
truncated
head.
In
central
nervous
system,
protein
primarily
derived
from
astrocytes,
but
also
produced
when
neurons
stressed
or
affected
certain
stress,
injury,
aging
conditions.
ApoE4
induces
tau
pathologies,
leading
neuroinflammation
damage,
impairing
learning
memory
functions.
However,
how
mediates
pathology
remains
unclear.
Recent
studies
shown
may
lead
greater
neurotoxicity,
which
increases
development.
This
review
focuses
pathophysiology
explains
deposition,
mechanisms
hyperphosphorylation,
potential
therapeutic
targets.
Alzheimer s Research & Therapy,
Год журнала:
2023,
Номер
15(1)
Опубликована: Март 14, 2023
Abstract
Background
CSF-soluble
platelet-derived
growth
factor
receptor
beta
(sPDGFRβ)
is
closely
associated
with
pericyte
damage.
However,
the
changes
in
CSF
sPDGFRβ
levels
and
their
role
blood
–
brain
barrier
(BBB)
leakage
at
different
stages
of
Alzheimer’s
disease
(AD),
or
without
cerebral
small
vessel
(CSVD)
burden,
remain
unclear.
Methods
A
total
158
individuals
from
China
Aging
Neurodegenerative
Disorder
Initiative
cohort
were
selected,
including
27,
48,
83
a
clinical
dementia
rating
(CDR)
score
0,
0.5,
1
2,
respectively.
tau,
phosphorylated
tau181
(p-tau181),
Aβ40,
Aβ42
measured
using
Simoa
assay.
Albumin
by
commercial
assay
kits.
CSVD
burden
was
assessed
magnetic
resonance
imaging.
Results
highest
level
CDR
0.5
group.
significantly
correlated
CSF/serum
albumin
ratio
(Q-alb)
0–0.5
group
(
β
=
0.314,
p
0.008)
but
not
1–2
−
0.117,
0.317).
In
group,
exhibited
significant
mediating
effect
between
Aβ42/Aβ40
Q-alb
0.038).
Q-alb,
rather
than
sPDGFRβ,
showed
difference
burden.
Furthermore,
higher
subjects
progressive
mild
cognitive
impairment
those
stable
<
0.001).
Meanwhile,
yearly
MMSE
scores
0.400,
0.020)
(A+)
subgroup
0.542,
0.019).
Conclusions
We
provide
evidence
that
increased
BBB
early
stage
AD,
which
may
contribute
to
AD
progression.
Science Bulletin,
Год журнала:
2023,
Номер
68(16), С. 1800 - 1808
Опубликована: Июль 11, 2023
Discrepancies
in
diagnostic
biomarkers
for
Alzheimer's
Disease
(AD)
may
arise
from
racial
disparities,
risk
factors,
or
lifestyle
differences.
Moreover,
there
has
been
a
lack
of
systematic
and
multicenter
studies
to
evaluate
baselines
the
AD
Chinese
populations.
Thus,
is
an
urgent
need
research
investigate
effectiveness
blood
AD,
specifically
Han
population,
using
approach.
In
present
multicenter-based
cross-sectional
longitudinal
study,
we
evaluated
817
samples
6
different
clinical
centers.
We
measured
plasma
amyloid
beta
(Aβ)-40,
Aβ42,
phosphorylated
tau
181
(pTau),
total
(tTau),
serum
neurofilament
light
(NFL),
glial
fibrillary
acidic
protein
(GFAP).
Additionally,
18F-florbetapir
positron
electron
tomography
magnetic
resonance
imaging
were
also
performed.
A
combination
APOE
genotype
with
pTau
GFAP
demonstrated
exceptional
performance
distinguishing
Aβ
status.
Furthermore,
baseline
levels
exhibited
strong
association
cognitive
decline
over
time
brain
atrophy,
higher
predicting
faster
rate
neurodegeneration.
summary,
these
results
validate
practicality
encompassing
various
regions
within
China.
they
emphasize
potential
as
non-invasive
methods
detecting
screening
at
early
stage.
Alzheimer s Research & Therapy,
Год журнала:
2024,
Номер
16(1)
Опубликована: Апрель 16, 2024
Abstract
Introduction
The
Guangdong-Hong
Kong-Macao
Greater-Bay-Area
of
South
China
has
an
86
million
population
and
faces
a
significant
challenge
Alzheimer’s
disease
(AD).
However,
the
characteristics
prevalence
AD
in
this
area
are
still
unclear
due
to
rarely
available
community-based
neuroimaging
cohort.
Methods
Following
standard
protocols
Disease
Neuroimaging
Initiative,
Healthy
Aging
Brain
Study
(GHABS)
was
initiated
2021.
GHABS
participants
completed
clinical
assessments,
plasma
biomarkers,
genotyping,
magnetic
resonance
imaging
(MRI),
β-amyloid
(Aβ)
positron
emission
tomography
(PET)
imaging,
tau
PET
imaging.
cohort
focuses
on
pathophysiology
characterization
early
detection
Greater
Bay
Area.
In
study,
we
analyzed
Aβ
42
/Aβ
40
(A),
p-Tau
181
(T),
neurofilament
light,
GFAP
by
Simoa
470
Chinese
older
adults,
301,
195,
70
had
MRI,
PET,
respectively.
Plasma
hippocampal
volume,
temporal-metaROI
cortical
thickness
were
compared
between
normal
control
(NC),
subjective
cognitive
decline
(SCD),
mild
impairment
(MCI),
dementia
groups,
controlling
for
age,
sex,
APOE-ε4
.
A/T
profiles
positivity
also
determined
different
diagnostic
groups.
Results
aims,
study
design,
data
collection,
potential
applications
summarized.
SCD
individuals
significantly
higher
than
NC
individuals.
MCI
patients
showed
more
abnormal
changes
all
biomarkers
frequencies
A+/T+
(NC;
5.9%,
SCD:
8.2%,
MCI:
25.3%,
dementia:
64.9%)
(NC:
25.6%,
22.5%,
47.7%,
89.3%)
reported.
Discussion
may
provide
helpful
guidance
toward
designing
community
cohorts
China.
This
first
time,
reported
atrophy,
AD-signature
thinning,
as
well
Area
These
findings
novel
insights
into
understanding
pathological
China’s
population.
Molecular Neurodegeneration,
Год журнала:
2024,
Номер
19(1)
Опубликована: Июль 30, 2024
Abstract
Background
It
is
not
fully
established
whether
plasma
β-amyloid(Aβ)
42
/Aβ
40
and
phosphorylated
Tau
181
(p-Tau
)
can
effectively
detect
Alzheimer’s
disease
(AD)
pathophysiology
in
older
Chinese
adults
how
these
biomarkers
correlate
with
astrocyte
reactivity,
Aβ
plaque
deposition,
tau
tangle
aggregation,
neurodegeneration.
Methods
We
recruited
470
analyzed
,
p-Tau
glial
fibrillary
acidic
protein
(GFAP),
neurofilament
light
(NfL)
using
the
Simoa
platform.
Among
them,
301,
195,
70
underwent
magnetic
resonance
imaging,
positron
emission
tomography
imaging.
The
thresholds
were
defined
as
≤0.0609
≥2.418
based
on
receiver
operating
characteristic
curve
analysis
Youden
index
by
comparing
Aβ-PET
negative
cognitively
unimpaired
individuals
positive
impaired
patients.
To
evaluate
feasibility
of
(A)
(T)
to
AD
understand
reactivity
affects
this
process,
we
compared
GFAP,
plaque,
tangle,
NfL,
hippocampal
volume,
temporal-metaROI
cortical
thickness
between
different
A/T
profiles
explored
their
relations
each
other
general
linear
models,
including
age,
sex,
APOE-ε4
diagnosis
covariates.
Results
Plasma
A+/T
+
showed
highest
levels
axonal
degeneration,
lowest
volume
thickness.
Lower
higher
independently
synergistically
correlated
GFAP
plaque.
Elevated
concentrations
directly
interactively
associated
more
formation.
Regarding
neurodegeneration,
strongly
measured
lower
related
greater
atrophy.
Higher
thinner
significantly
interacted
predicting
thinning.
Voxel-wise
imaging
confirmed
findings.
Discussion
This
study
provides
a
valuable
reference
for
community
population
offers
novel
insights
into
contributes
progression,
highlighting
importance
targeting
reactive
astrogliosis
prevent
AD.