EBioMedicine,
Journal Year:
2025,
Volume and Issue:
112, P. 105557 - 105557
Published: Jan. 31, 2025
Synapse
preservation
is
key
for
healthy
cognitive
ageing,
and
synapse
loss
represents
a
critical
anatomical
basis
of
dysfunction
in
Alzheimer's
disease
(AD),
predicting
dementia
onset,
severity,
progression.
viewed
as
primary
pathologic
event,
preceding
neuronal
brain
atrophy
AD.
Synapses
may,
therefore,
represent
one
the
earliest
clinically
most
meaningful
targets
neuropathologic
processes
driving
AD
dementia.
The
highly
selective
particularly
vulnerable
synapses
while
leaving
others,
termed
resilient,
largely
unaffected.
Yet,
anatomic
molecular
hallmarks
resilient
populations
their
association
with
changes
(e.g.
amyloid-β
plaques
tau
tangles)
memory
remain
poorly
understood.
Characterising
selectively
may
be
to
understanding
mechanisms
versus
enable
development
robust
biomarkers
disease-modifying
therapies
Life,
Journal Year:
2025,
Volume and Issue:
15(1), P. 96 - 96
Published: Jan. 14, 2025
Recent
research
highlights
compelling
links
between
oral
health,
particularly
periodontitis,
and
systemic
diseases,
including
Alzheimer's
disease
(AD).
Although
the
biological
mechanisms
underlying
these
associations
remain
unclear,
role
of
periodontal
pathogens,
Porphyromonas
gingivalis,
has
garnered
significant
attention.
P.
a
major
driver
is
recognized
for
its
potential
effects
putative
in
AD
pathogenesis.
This
review
examines
evidence
connecting
gingivalis
to
hallmark
features,
such
as
amyloid
β
accumulation,
tau
hyperphosphorylation,
neuroinflammation,
other
neuropathological
features
consistent
with
AD.
Virulence
factors,
gingipains
lipopolysaccharides,
were
shown
be
implicated
blood-brain
barrier
disruption,
neuronal
damage.
gingivalis-derived
outer
membrane
vesicles
may
serve
disseminate
virulence
factors
brain
tissues.
Indirect
mechanisms,
inflammation
triggered
by
chronic
infections,
are
also
supposed
exacerbate
neurodegenerative
processes.
While
exact
pathways
uncertain,
studies
detecting
components
AD-affected
brains
support
their
possible
underscores
need
further
investigation
into
gingivalis-mediated
interplay
host
responses.
Understanding
interactions
could
provide
critical
insights
novel
strategies
reducing
risk
through
management.
Expert Opinion on Drug Metabolism & Toxicology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 28
Published: Jan. 21, 2025
Genetic
load
influences
the
therapeutic
response
to
conventional
drugs
in
Alzheimer's
disease
(AD).
Pharmacogenetics
(PGx)
is
best
option
reduce
drug-drug
interactions
and
adverse
drug
reactions
patients
undergoing
polypharmacy
regimens.
However,
there
are
important
limitations
that
make
it
difficult
incorporate
pharmacogenetics
into
routine
clinical
practice.
This
article
analyzes
pharmacogenetic
apparatus
made
up
of
pathogenic,
mechanistic,
metabolic,
transporter,
pleiotropic
genes
responsible
for
efficacy
safety
pharmacological
treatment,
impact
genetic
on
outcome
multifactorial
treatments,
practical
aspects
effective
use
PGx.
Over
120
closely
associated
with
AD.
There
an
accumulation
cerebrovascular
(CVn)
neurodegenerative
(ADn)
APOE-4
carriers
accumulate
more
deleterious
related
other
CVn
ADn
genes,
develop
earlier,
at
a
biological
disadvantage
compared
non-carriers.
CYP2D6-PMs
worst
responders
anti-dementia
drugs.
Some
hinder
implementation
PGx
practice,
including
lack
information
many
drugs,
low
number
screening
protocols,
educational
deficiencies
medical
community
regarding
genomic
medicine.
Neurology Genetics,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: Jan. 29, 2025
Alzheimer
disease
(AD),
the
most
common
dementing
syndrome
in
United
States,
is
currently
established
by
presence
of
amyloid-β
and
tau
protein
biomarkers
setting
clinical
cognitive
impairment.
These
straightforward
diagnostic
parameters
belie
an
immense
complexity
genetic
architecture
underlying
risk
presentation
AD.
In
this
review,
we
provide
a
focused
overview
current
state
AD
genetics.
We
discuss
discovery
familial
autosomal
dominant
genes,
identification
candidate
genes
associated
with
AD,
variants
conferring
higher
developing
compared
general
population.
particular,
important
features
due
to
APOE
ε4
allele.
addition
risk,
describe
how
field
has
made
headway
understanding
factors
that
may
protect
from
The
biological
implications
practical
limitations
information
gleaned
genome-wide
association
studies
over
years
are
also
discussed.
readers
will
have
up-to-date
where
our
efforts
understand
layers
EBioMedicine,
Journal Year:
2025,
Volume and Issue:
112, P. 105557 - 105557
Published: Jan. 31, 2025
Synapse
preservation
is
key
for
healthy
cognitive
ageing,
and
synapse
loss
represents
a
critical
anatomical
basis
of
dysfunction
in
Alzheimer's
disease
(AD),
predicting
dementia
onset,
severity,
progression.
viewed
as
primary
pathologic
event,
preceding
neuronal
brain
atrophy
AD.
Synapses
may,
therefore,
represent
one
the
earliest
clinically
most
meaningful
targets
neuropathologic
processes
driving
AD
dementia.
The
highly
selective
particularly
vulnerable
synapses
while
leaving
others,
termed
resilient,
largely
unaffected.
Yet,
anatomic
molecular
hallmarks
resilient
populations
their
association
with
changes
(e.g.
amyloid-β
plaques
tau
tangles)
memory
remain
poorly
understood.
Characterising
selectively
may
be
to
understanding
mechanisms
versus
enable
development
robust
biomarkers
disease-modifying
therapies
