Cell Reports,
Год журнала:
2020,
Номер
30(13), С. 4418 - 4432.e4
Опубликована: Март 1, 2020
Brain
endothelial
cells
(BECs)
are
key
constituents
of
the
blood-brain
barrier
(BBB),
protecting
brain
from
pathogens
and
restricting
access
circulatory
factors.
Yet,
because
proteins
have
prominent
age-related
effects
on
adult
neurogenesis,
neuroinflammation,
cognitive
function
in
mice,
we
wondered
whether
BECs
receive
potentially
relay
signals
between
blood
brain.
Using
single-cell
RNA
sequencing
hippocampal
BECs,
discover
that
capillary
BECs—compared
with
arterial
venous
BECs—undergo
greatest
transcriptional
changes
normal
aging,
upregulating
innate
immunity
oxidative
stress
response
pathways.
Short-term
infusions
aged
plasma
into
young
mice
recapitulate
aspects
this
aging
transcriptome,
remarkably,
exert
rejuvenation
transcriptome.
Together,
these
findings
suggest
age
is
exquisitely
sensitive
to
cues
pinpoint
BBB
itself
as
a
promising
therapeutic
target
treat
disease.
Cold Spring Harbor Perspectives in Medicine,
Год журнала:
2012,
Номер
2(4), С. a006213 - a006213
Опубликована: Янв. 31, 2012
Imaging
has
played
a
variety
of
roles
in
the
study
Alzheimer
disease
(AD)
over
past
four
decades.
Initially,
computed
tomography
(CT)
and
then
magnetic
resonance
imaging
(MRI)
were
used
diagnostically
to
rule
out
other
causes
dementia.
More
recently,
modalities
including
structural
functional
MRI
positron
emission
(PET)
studies
cerebral
metabolism
with
fluoro-deoxy-d-glucose
(FDG)
amyloid
tracers
such
as
Pittsburgh
Compound-B
(PiB)
have
shown
characteristic
changes
brains
patients
AD,
prodromal
even
presymptomatic
states
that
can
help
rule-in
AD
pathophysiological
process.
No
one
modality
serve
all
purposes
each
unique
strengths
weaknesses.
These
their
particular
utilities
are
discussed
this
article.
The
challenge
for
future
will
be
combine
biomarkers
most
efficiently
facilitate
diagnosis,
staging,
and,
importantly,
development
effective
disease-modifying
therapies.
Current Neuropharmacology,
Год журнала:
2020,
Номер
18(11), С. 1106 - 1125
Опубликована: Май 28, 2020
The
only
conclusive
way
to
diagnose
Alzheimer's
is
carry
out
brain
autopsy
of
the
patient's
tissue
and
ascertain
whether
subject
had
or
any
other
form
dementia.
However,
due
non-feasibility
such
methods,
conclude
conditions,
medical
practitioners
use
tests
that
examine
a
mental
ability.Accurate
diagnosis
at
an
early
stage
need
hour
for
initiation
therapy.
cause
most
cases
still
remains
unknown
except
where
genetic
distinctions
have
been
observed.
Thus,
standard
drug
regimen
ensues
in
every
patient,
irrespective
cause,
which
may
not
always
be
beneficial
halting
reversing
disease
progression.
To
provide
better
life
patients
by
suppressing
existing
symptoms,
diagnosis,
curative
therapy,
site-specific
delivery
drugs,
application
hyphenated
methods
like
artificial
intelligence
brought
into
main
field
therapeutics.In
this
review,
we
compiled
hypotheses
explain
disease,
highlighted
gene
immunotherapy,
peptidomimetics,
metal
chelators,
probiotics
quantum
dots
as
advancements
strategies
manage
Alzheimer's.Biomarkers,
brain-imaging,
theranostics,
along
with
intelligence,
are
understood
future
management
Alzheimer's.
Brain,
Год журнала:
2007,
Номер
130(10), С. 2616 - 2635
Опубликована: Авг. 19, 2007
Distinguishing
Alzheimer's
disease
(AD)
and
frontotemporal
dementia
(FTD)
currently
relies
on
a
clinical
history
examination,
but
positron
emission
tomography
with
[(18)F]
fluorodeoxyglucose
(FDG-PET)
shows
different
patterns
of
hypometabolism
in
these
disorders
that
might
aid
differential
diagnosis.
Six
experts
variable
FDG-PET
experience
made
independent,
forced
choice,
diagnostic
decisions
45
patients
pathologically
confirmed
AD
(n
=
31)
or
FTD
14)
using
five
separate
methods:
(1)
review
summaries,
(2)
checklist
alone,
(3)
summary
checklist,
(4)
transaxial
scans
(5)
stereotactic
surface
projection
(SSP)
metabolic
statistical
maps.
In
addition,
we
evaluated
the
effect
sequential
followed
by
SSP.
Visual
interpretation
SSP
images
was
superior
to
assessment
had
best
inter-rater
reliability
(mean
kappa
0.78)
accuracy
(89.6%).
It
also
highest
specificity
(97.6%)
sensitivity
(86%),
positive
likelihood
ratio
for
(36.5).
The
addition
summaries
increased
confidence
both
FTD.
particularly
helpful
when
raters
were
uncertain
their
after
brief
training
is
more
reliable
accurate
distinguishing
from
than
methods
alone.
adds
important
information
appropriately
increases
confidence,
even
among
experienced
specialists.
Cold Spring Harbor Perspectives in Medicine,
Год журнала:
2012,
Номер
2(6), С. a006262 - a006262
Опубликована: Фев. 21, 2012
Colin
L.
Masters1
and
Dennis
J.
Selkoe2
The
Mental
Health
Research
Institute,
University
of
Melbourne,
Parkville
3010,
Australia
Center
for
Neurologic
Diseases,
Harvard
Medical
School
Brigham
Women's
Hospital,
Boston,
Massachusetts
02115
Correspondence:
c.masters{at}unimelb.edu.au
Alzheimer s & Dementia,
Год журнала:
2014,
Номер
11(1), С. 58 - 69
Опубликована: Май 2, 2014
Several
potential
disease-modifying
drugs
for
Alzheimer's
disease
(AD)
have
failed
to
show
any
effect
on
progression
in
clinical
trials,
conceivably
because
the
AD
subjects
are
already
too
advanced
derive
benefit
from
treatment
and
diagnosis
based
criteria
alone
introduces
a
high
misdiagnosis
rate.
Thus,
well-validated
biomarkers
early
detection
accurate
crucial.
Low
cerebrospinal
fluid
(CSF)
concentrations
of
amyloid-β
(Aβ1-42)
peptide,
combination
with
total
tau
phosphorylated
tau,
sensitive
specific
highly
predictive
dementia
patients
mild
cognitive
impairment.
However,
interlaboratory
variations
results
seen
currently
available
immunoassays
concern.
Recent
worldwide
standardization
efforts
quality
control
programs
include
standard
operating
procedures
both
preanalytical
(e.g.,
lumbar
puncture
sample
handling)
analytical
preparation
calibration
curve)
procedures.
Efforts
also
ongoing
develop
reproducible
assays
fully
automated
instruments.
These
global
harmonization
measures
will
provide
basis
generalized
international
application
CSF
trials
routine
AD.
The Journal of Prevention of Alzheimer s Disease,
Год журнала:
2021,
Номер
unknown, С. 1 - 16
Опубликована: Янв. 1, 2021
Alzheimer’s
disease
is
a
progressive,
irreversible
neurodegenerative
impacting
cognition,
function,
and
behavior.
progresses
along
continuum
from
preclinical
disease,
to
mild
cognitive
and/or
behavioral
impairment
then
dementia.
Recently,
clinicians
have
been
encouraged
diagnose
earlier,
before
patients
progressed
The
early
accurate
detection
of
disease-associated
symptoms
underlying
pathology
by
fundamental
for
the
screening,
diagnosis,
subsequent
management
patients.
It
also
enables
their
caregivers
plan
future
make
appropriate
lifestyle
changes
that
could
help
maintain
quality
life
longer.
Unfortunately,
detecting
early-stage
in
clinical
practice
can
be
challenging
hindered
several
barriers
including
constraints
on
clinicians’
time,
difficulty
accurately
diagnosing
pathology,
healthcare
providers
often
dismiss
as
part
normal
aging
process.
As
prevalence
this
continues
grow,
current
model
diagnosis
patient
will
need
evolve
integrate
care
across
disciplines
continuum,
beginning
with
primary
care.
This
review
summarizes
importance
establishing
an
related
practical
‘how-to’
guidance
considerations,
tools
used
throughout
diagnostic
journey.
Combination
antiretroviral
therapy,
despite
being
potent
and
life-prolonging,
is
not
curative
does
eradicate
HIV-1
infection
since
interruption
of
treatment
inevitably
results
in
a
rapid
rebound
viremia.
Reactivation
latently
infected
cells
harboring
transcriptionally
silent
but
replication-competent
proviruses
potential
source
persistent
residual
viremia
cART-treated
patients.
Although
multiple
reservoirs
may
exist,
the
persistence
resting
CD4+
T
carrying
latent
represents
major
barrier
to
eradication.
In
this
review,
we
will
discuss
latest
reports
on
molecular
mechanisms
that
regulate
latency
at
transcriptional
level,
including
interference,
role
cellular
factors,
chromatin
organization
epigenetic
modifications,
viral
Tat
trans-activator
its
cofactors.
Since
also
operate
post-transcriptional
consider
inhibition
nuclear
RNA
export
translation
by
microRNAs
as
barriers
gene
expression.
Finally,
review
therapeutic
approaches
clinical
studies
aimed
achieving
either
sterilizing
cure
or
functional
infection,
with
special
emphasis
most
recent
pharmacological
strategies
reactivate
viruses
decrease
pool
reservoirs.