Alzheimer s Research & Therapy,
Journal Year:
2024,
Volume and Issue:
16(1)
Published: July 27, 2024
Abstract
Background
Sex
differences
in
neuroinflammation
could
contribute
to
women’s
increased
risk
of
Alzheimer’s
disease
(AD),
providing
rationale
for
exploring
sex-specific
AD
biomarkers.
In
AD,
dysregulation
the
kynurenine
pathway
(KP)
contributes
and
there
is
some
evidence
sex
KP
metabolism.
However,
associations
between
metabolism
biomarkers
need
be
explored
further.
Methods
Here
we
investigate
cerebrospinal
fluid
concentrations
seven
metabolites
with
established
neopterin,
an
indicator
neuroinflammation.
This
study
included
311
patients
symptomatic
105
age-matched
cognitively
unimpaired
(CU)
controls,
followed
up
5
years.
Results
We
found
group,
higher
levels
most
men,
while
were
no
CU
group.
line
this,
more
significantly
altered
men
compared
was
a
trend
same
direction
women.
Furthermore,
kynurenic
acid
acid/quinolinic
ratio
but
clinical
progression.
Discussion
our
cohort,
restricted
patients.
Our
results
suggest
that
due
inflammation
Frontiers in Aging Neuroscience,
Journal Year:
2022,
Volume and Issue:
14
Published: Oct. 10, 2022
Background
With
the
increase
in
aging
population
worldwide,
Alzheimer's
disease
has
become
a
rapidly
increasing
public
health
concern.
Monitoring
dementia
burden
will
support
development
strategies
by
providing
scientific
data.
Methods
Based
on
data
obtained
from
2019
Global
Burden
of
Disease
(GBD)
database,
numbers
and
age-standardized
rates
(ASRs)
incidence,
prevalence,
death,
disability-adjusted
life-years
(DALYs)
other
dementias
1990
to
were
analyzed.
Calculated
estimated
annual
percentage
changes
(EAPCs)
Joinpoint
regression
analyses
performed
evaluate
trends
during
this
period.
We
also
evaluated
correlations
between
epidemiology
sociodemographic
index
(SDI),
an
indicator
level
social
country
or
region
considering
education
rate,
economic
situation,
total
fertility
rate.
Results
From
2019,
incidence
prevalence
increased
147.95
160.84%,
respectively.
The
ASR
DALYs
both
men
women
consistently
over
study
All
ASRs
higher
than
those
men,
but
increases
more
pronounced
men.
In
addition,
positively
correlated
with
SDI.
Moreover,
proportion
patients
70
years
old
was
SDI
level.
Smoking
major
risk
factor
for
while
obesity
women.
Conclusion
worldwide.
This
trend
serious
high-SDI
areas,
especially
among
elderly
populations
who
should
receive
additional
attention.
Policy-makers
take
steps
reverse
situation.
Notably,
at
disease,
showed
faster
increase.
give
attention
population,
attach
importance
interventions
targeting
factors,
formulate
action
plans
address
dementia.
Alzheimer s Research & Therapy,
Journal Year:
2023,
Volume and Issue:
15(1)
Published: Jan. 9, 2023
Abstract
Background
The
risk
of
dementia
is
higher
in
women
than
men.
metabolic
consequences
estrogen
decline
during
menopause
accelerate
neuropathology
women.
use
hormone
replacement
therapy
(HRT)
the
prevention
cognitive
has
shown
conflicting
results.
Here
we
investigate
modulating
role
APOE
genotype
and
age
at
HRT
initiation
on
heterogeneity
response
to
HRT.
Methods
analysis
used
baseline
data
from
participants
European
Prevention
Alzheimer’s
Dementia
(EPAD)
cohort
(total
n
=
1906,
women=
1178,
61.8%).
Analysis
covariate
(ANCOVA)
models
were
employed
test
independent
interactive
impact
select
tests,
such
as
MMSE,
RBANS,
dot
counting,
Four
Mountain
Test
(FMT),
supermarket
trolley
(SMT),
together
with
volumes
medial
temporal
lobe
(MTL)
regions
by
MRI.
Multiple
linear
regression
examine
according
APOE4
carrier
status
these
MRI
outcomes.
Results
users
had
highest
RBANS
delayed
memory
index
score
(P-
*HRT
interaction
0.009)
compared
non-users
non-
carriers,
6–10%
larger
entorhinal
(left)
amygdala
(right
left)
(
P
-interaction=
0.002,
0.003,
0.005
respectively).
Earlier
introduction
was
associated
right
(standardized
β
−0.555,
p
=0.035)
left
hippocampal
−0.577,
=0.028)
only
carriers.
Conclusion
improved
carriers
only.
This
may
represent
an
effective
targeted
strategy
mitigate
life-time
AD
this
large
at-risk
population
subgroup.
Confirmation
findings
a
fit
for
purpose
RCT
prospective
recruitment
based
needed
establish
causality.
Physiological Reviews,
Journal Year:
2023,
Volume and Issue:
104(1), P. 103 - 197
Published: Oct. 16, 2023
Alzheimer
disease
(AD)
is
associated
with
multiple
etiologies
and
pathological
mechanisms,
among
which
oxidative
stress
(OS)
appears
as
a
major
determinant.
Intriguingly,
OS
arises
in
various
pathways
regulating
brain
functions,
it
seems
to
link
different
hypotheses
mechanisms
of
AD
neuropathology
high
fidelity.
The
particularly
vulnerable
damage,
mainly
because
its
unique
lipid
composition,
resulting
an
amplified
cascade
redox
reactions
that
target
several
cellular
components/functions
ultimately
leading
neurodegeneration.
present
review
highlights
the
“OS
hypothesis
AD,”
including
amyloid
beta-peptide-associated
role
protein
oxidation
unraveled
by
proteomics,
antioxidant
strategies
have
been
investigated
modulate
progression
AD.
Collected
studies
from
our
groups
others
contributed
unraveling
close
relationships
between
perturbation
homeostasis
elucidating
redox-regulated
events
potentially
involved
both
pathogenesis
However,
complexity
requires
in-depth
understanding
intracellular
affecting
relevant
for
functions.
This
crucial
developing
pharmacological
targeting
OS-mediated
toxicity
may
contribute
slow
well
improve
quality
life
persons
this
severe
dementing
disorder.
Nature Neuroscience,
Journal Year:
2023,
Volume and Issue:
26(6), P. 1008 - 1020
Published: May 11, 2023
Molecular
diversity
of
microglia,
the
resident
immune
cells
in
CNS,
is
reported.
Whether
microglial
subsets
characterized
by
expression
specific
proteins
constitute
subtypes
with
distinct
functions
has
not
been
fully
elucidated.
Here
we
describe
a
subtype
expressing
enzyme
arginase-1
(ARG1;
that
is,
ARG1+
microglia)
found
predominantly
basal
forebrain
and
ventral
striatum
during
early
postnatal
mouse
development.
microglia
are
enriched
phagocytic
inclusions
exhibit
molecular
signature,
including
upregulation
genes
such
as
Apoe,
Clec7a,
Igf1,
Lgals3
Mgl2,
compared
to
ARG1-
microglia.
Microglial-specific
knockdown
Arg1
results
deficient
cholinergic
innervation
impaired
dendritic
spine
maturation
hippocampus
where
neurons
project,
which
turn
long-term
potentiation
cognitive
behavioral
deficiencies
female
mice.
Our
expand
on
provide
insights
into
subtype-specific
functions.
Alzheimer s & Dementia,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 9, 2025
Abstract
INTRODUCTION
Menopausal
hormone
therapy
(MHT),
along
with
the
apolipoprotein
E
(
APOE
)
ε4
allele,
has
been
suggested
as
a
possible
risk
factor
for
Alzheimer's
disease
(AD).
However,
relationship
between
MHT
and
cerebrospinal
fluid
(CSF)
biomarkers
is
unknown:
we
investigated
this
association,
whether
carrier
status
moderates
it.
METHODS
In
an
observational
study
of
136
cognitively
unimpaired
female
participants
M
age
=
66.0;
standard
deviation
6.3),
examined
use
alone
or
in
interaction
was
associated
CSF
levels
phosphorylated
tau
(p‐tau),
amyloid
beta
(Aβ)40,
Aβ42,
p‐tau/Aβ42,
Aβ42/40
ratios.
RESULTS
Significant
interactions
were
found
biomarkers.
carriers
who
users
showed
worse
p‐tau/Aβ42
ratios
than
all
other
non‐users.
DISCUSSION
The
presence
both
may
be
elevated
deposition
AD
pathology
sample
demonstrated
high
familial
risk.
Highlights
menopausal
(MHT)
(p‐tau)/amyloid
(Aβ)42
non‐users
non‐carriers,
Younger
at
initiation
only.
carriage
pathology.
Further
studies
larger
sizes
are
necessary
to
confirm
differences
observed
current
study.
Alzheimer s & Dementia,
Journal Year:
2022,
Volume and Issue:
19(2), P. 671 - 695
Published: Nov. 19, 2022
Abstract
This
review
summarizes
recent
evidence
on
how
mid‐life
hypertension,
hyperhomocysteinemia
(HHcy)
and
blood
pressure
variability,
as
well
late‐life
hypotension,
exacerbate
Alzheimer's
disease
(AD)
dementia
risk.
Intriguingly,
HHcy
also
increases
the
risk
for
revealing
importance
of
understanding
relationship
between
comorbid
cardiovascular
factors.
Hypertension‐induced
presents
more
evidently
in
women,
highlighting
relevance
sex
differences
impact
We
summarize
each
major
antihypertensive
drug
class's
effects
cognitive
impairment
AD
pathology,
carbonic
anhydrase
inhibitors,
diuretics
modulating
cerebral
flow,
have
recently
gained
preclinical
promising
treatment
against
AD.
report
novel
vascular
biomarkers
risk,
those
associated
with
hypertension
HHcy.
Importantly,
we
propose
that
future
studies
should
consider
potential
contributors
to
impairment,
uncovering
underlying
molecular
mechanisms
would
aid
identification
preventive
strategies.
Archives of Toxicology,
Journal Year:
2023,
Volume and Issue:
98(1), P. 95 - 119
Published: Nov. 15, 2023
Abstract
Life
expectancy
has
increased
immensely
over
the
past
decades,
bringing
new
challenges
to
health
systems
as
advanced
age
increases
predisposition
for
many
diseases.
One
of
those
is
burden
neurologic
disorders.
While
hypotheses
have
been
placed
explain
aging
mechanisms,
it
widely
accepted
that
increasing
pro-inflammatory
status
with
or
“inflammaging”
a
main
determinant
biological
aging.
Furthermore,
inflammaging
at
cornerstone
age-related
diseases
and
its
involvement
in
disorders
an
exciting
hypothesis.
Indeed,
development
elderly
seem
share
some
basic
pathways
fundamentally
converge
on
inflammation.
Peripheral
inflammation
significantly
influences
brain
function
contributes
neurological
disorders,
including
Alzheimer’s
disease,
Parkinson’s
multiple
sclerosis.
Understanding
role
pathogenesis
progressive
crucial
importance
developing
effective
treatments
interventions
can
slow
down
prevent
disease
progression,
therefore,
decreasing
social
economic
burden.
