Alzheimer s Research & Therapy,
Год журнала:
2020,
Номер
12(1)
Опубликована: Май 13, 2020
Abstract
Background
The
panel
of
fluid-
and
imaging-based
biomarkers
available
for
neurodegenerative
disease
research
is
growing
has
the
potential
to
close
important
gaps
in
clinic.
With
this
growth
increasing
use,
appropriate
implementation
interpretation
are
paramount.
Various
feature
nuanced
differences
strengths,
limitations,
biases
that
must
be
considered
when
investigating
etiology
clinical
utility.
For
example,
neuropathological
investigations
Alzheimer’s
pathogenesis
can
fall
disagreement
with
conclusions
reached
by
biomarker-based
investigations.
Considering
varied
different
methodologies
approaches
may
help
harmonize
disciplines
within
field.
Purpose
review
Along
separate
articles
covering
fluid
imaging
issue
Research
Therapy
,
we
present
result
a
discussion
from
2019
Biomarkers
Neurodegenerative
Diseases
course
at
University
College
London.
Here,
discuss
themes
biomarker
use
research,
commenting
on
interpretation,
considerations
across
diseases.
We
also
draw
attention
areas
where
combined
other
understand
issues
pathophysiology
underlying
dementia.
Lastly,
highlight
novel
modalities
have
been
proposed
landscape
care.
Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Авг. 8, 2019
How
are
memories
transferred
from
short-term
to
long-term
storage?
Systems-level
memory
consolidation
is
thought
be
dependent
on
the
coordinated
interplay
of
cortical
slow
waves,
thalamo-cortical
sleep
spindles
and
hippocampal
ripple
oscillations.
However,
it
currently
unclear
how
selective
interaction
these
cardinal
oscillations
organized
support
information
reactivation
transfer.
Here,
using
human
intracranial
recordings,
we
demonstrate
that
prefrontal
cortex
plays
a
key
role
in
organizing
ripple-mediated
transfer
during
non-rapid
eye
movement
(NREM)
sleep.
We
reveal
temporally
precise
form
coupling
between
slow-wave
spindle
oscillations,
which
actively
dictates
hippocampal-neocortical
dialogue
Our
results
suggest
model
sleeping
brain
rapid
bidirectional
interactions,
triggered
by
cortex,
mediate
activation
optimally
time
subsequent
neocortex
NREM
Brain,
Год журнала:
2023,
Номер
146(3), С. 842 - 849
Опубликована: Янв. 19, 2023
After
years
of
failed
attempts
to
develop
a
disease-modifying
therapy
for
Alzheimer's
disease,
consistent
evidence
in
support
clinical
efficacy
was
finally
presented
monoclonal
antibody
targeting
the
amyloid-β
protofibrils.
In
addition
meeting
primary
outcome
slowing
disease
progression
over
18
months,
secondary
outcomes
and
lowering
on
PET
also
underpin
positive
results
trial.
this
opinion
piece,
we
highlight
key
characteristics
previous
unsuccessful
trials
analyse
potential
reasons
why
those
treatment
early
failed.
We
compare
safety
profiles
different
antibodies
cautionary
measures
their
routine
use.
Last,
discuss
role
blood-based
biomarkers
transforming
care
pathway
facilitate
uptake
treatments,
proposing
an
integrated
case-finding
model
crossing
healthcare
sectors.
Taken
together,
real
breakthrough
may
have
been
achieved
by
proving
that
reduction
benefits,
rather
than
just
biomarker
changes.
At
same
time,
use
new
generation
drugs
will
show
if
statistical
translates
into
clinically
meaningful
change.
This
be
beginning
era
drug
development.
Precise
temporal
coordination
of
slow
oscillations
(SO)
and
sleep
spindles
is
a
fundamental
mechanism
sleep-dependent
memory
consolidation.
SO
spindle
morphology
changes
considerably
throughout
development.
Critically,
it
remains
unknown
how
the
precise
these
two
develops
during
brain
maturation
whether
their
synchronization
indexes
development
networks.
Here,
we
use
longitudinal
study
design
spanning
from
childhood
to
adolescence,
where
participants
underwent
polysomnography
performed
declarative
word-pair
learning
task.
Performance
on
task
was
better
adolescence.
After
disentangling
oscillatory
components
1/f
activity,
found
frequency
shifts
within
bands.
Consequently,
devised
an
individualized
cross-frequency
coupling
approach,
which
demonstrates
that
SO-spindle
strength
increases
maturation.
this
increase
indicated
enhanced
formation
Our
results
provide
evidence
improved
between
SOs
Neurobiology of Disease,
Год журнала:
2020,
Номер
144, С. 105031 - 105031
Опубликована: Июль 29, 2020
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
disorder
characterized
by
an
asymptomatic
period
of
amyloid-β
(Aβ)
deposition
as
insoluble
extracellular
plaque,
intracellular
tau
aggregation,
neuronal
and
synaptic
loss,
subsequent
cognitive
dysfunction
dementia.
A
growing
public
health
crisis,
the
worldwide
prevalence
AD
expected
to
rise
from
46.8
million
individuals
affected
in
2015
131.5
2050.
Sleep
disturbances
have
been
associated
with
increased
future
risk
AD.
bi-directional
relationship
hypothesized
between
sleep
either
markers
for
pathology
and/or
mechanism
mediating
In
this
review,
evidence
humans
supporting
complex
will
be
discussed
well
therapeutic
potential
challenges
treating
prevent
or
delay
onset
Brain,
Год журнала:
2021,
Номер
144(9), С. 2852 - 2862
Опубликована: Июль 15, 2021
Sleep
monitoring
may
provide
markers
for
future
Alzheimer's
disease;
however,
the
relationship
between
sleep
and
cognitive
function
in
preclinical
early
symptomatic
disease
is
not
well
understood.
Multiple
studies
have
associated
short
long
times
with
impairment.
Since
risk
of
change
age,
a
greater
understanding
how
cognition
changes
over
time
needed.
In
this
study,
we
hypothesized
that
longitudinal
will
non-linear
total
time,
spent
non-REM
REM
sleep,
efficiency
slow
wave
activity.
To
test
hypothesis,
monitored
sleep-wake
activity
4-6
nights
100
participants
who
underwent
standardized
testing
longitudinally,
APOE
genotyping,
measurement
biomarkers,
tau
amyloid-β42
CSF.
assess
function,
individuals
completed
neuropsychological
battery
at
each
clinical
visit
included
Free
Cued
Selective
Reminding
test,
Logical
Memory
Delayed
Recall
assessment,
Digit
Symbol
Substitution
Mini-Mental
State
Examination.
Performance
on
these
four
tests
was
Z-scored
within
cohort
averaged
to
calculate
Alzheimer
composite
score.
We
estimated
effect
cross-sectional
parameters
performance
using
generalized
additive
mixed
effects
models.
Generalized
models
allow
non-parametric
model
fitting
are
simply
linear
models;
predictors
constant
values
but
rather
sum
spline
fits.
found
measured
by
decreased
low
high
(P
<
0.001),
0.001)
0.01)
<1
Hz
1-4.5
even
after
adjusting
CSF
tau/amyloid-β42
ratio,
ε4
carrier
status,
years
education
sex.
Cognitive
stable
middle
range
activity,
suggesting
certain
levels
important
maintaining
function.
Although
interventional
needed,
diagnosing
treating
disturbances
optimize
stabilizing
or
disease.
