Frontiers in Neuroscience,
Год журнала:
2019,
Номер
13
Опубликована: Июнь 21, 2019
Alzheimer
disease
(AD)
represents
an
oncoming
epidemic
that
without
effective
treatment
promises
to
exact
extraordinary
human
and
financial
burdens.
Studies
of
pathogenesis
are
essential
for
defining
targets
discovering
disease-modifying
treatments.
Past
studies
AD
neuropathology
provided
valuable,
albeit
limited,
insights.
Nevertheless,
building
on
these
findings,
recent
have
increasingly
rich
harvest
genetic,
molecular
cellular
data
creating
unprecedented
opportunities
both
understand
treat
AD.
Among
the
most
significant
those
documenting
presence
within
brain
toxic
oligomeric
species
Aβ
tau.
Existing
support
view
such
can
propagate
spread
neural
circuits.
To
place
findings
in
context
we
first
review
genetics
AD,
including
Down
syndrome.
We
detail
existence
while
noting
unanswered
questions
concerning
their
precise
structures,
means
by
which
they
undergo
amplification
how
induce
neuronal
dysfunction
degeneration.
conclude
offering
a
speculative
synthesis
oligomers
tau
initiate
drive
pathogenesis.
While
100
years
after
Alzheimer's
report
there
is
much
still
learn
about
discovery
treatments,
application
new
concepts
sophisticated
tools
poised
deliver
important
advances
combatting
Nature Genetics,
Год журнала:
2022,
Номер
54(4), С. 412 - 436
Опубликована: Апрель 1, 2022
Abstract
Characterization
of
the
genetic
landscape
Alzheimer’s
disease
(AD)
and
related
dementias
(ADD)
provides
a
unique
opportunity
for
better
understanding
associated
pathophysiological
processes.
We
performed
two-stage
genome-wide
association
study
totaling
111,326
clinically
diagnosed/‘proxy’
AD
cases
677,663
controls.
found
75
risk
loci,
which
42
were
new
at
time
analysis.
Pathway
enrichment
analyses
confirmed
involvement
amyloid/tau
pathways
highlighted
microglia
implication.
Gene
prioritization
in
loci
identified
31
genes
that
suggestive
genetically
processes,
including
tumor
necrosis
factor
alpha
pathway
through
linear
ubiquitin
chain
assembly
complex.
also
built
score
with
future
AD/dementia
or
progression
from
mild
cognitive
impairment
to
AD/dementia.
The
improvement
prediction
led
1.6-
1.9-fold
increase
lowest
highest
decile,
addition
effects
age
APOE
ε4
allele.
Chemical Reviews,
Год журнала:
2018,
Номер
118(4), С. 1917 - 1950
Опубликована: Янв. 31, 2018
Extracellular
vesicles
(EVs)
are
diverse,
nanoscale
membrane
actively
released
by
cells.
Similar-sized
can
be
further
classified
(e.g.,
exosomes,
microvesicles)
based
on
their
biogenesis,
size,
and
biophysical
properties.
Although
initially
thought
to
cellular
debris,
thus
under-appreciated,
EVs
now
increasingly
recognized
as
important
vehicles
of
intercellular
communication
circulating
biomarkers
for
disease
diagnoses
prognosis.
Despite
clinical
potential,
the
lack
sensitive
preparatory
analytical
technologies
poses
a
barrier
translation.
New
platforms
including
molecular
ones
being
developed
address
these
challenges.
Recent
advances
in
field
expected
have
far-reaching
impact
both
basic
translational
studies.
This
article
aims
present
comprehensive
critical
overview
emerging
EV
detection
applications.
Cold Spring Harbor Perspectives in Medicine,
Год журнала:
2012,
Номер
2(7), С. a006338 - a006338
Опубликована: Март 13, 2012
Lennart
Mucke1
and
Dennis
J.
Selkoe2
Gladstone
Institute
of
Neurological
Disease
University
California,
San
Francisco,
California
94102
Center
for
Neurologic
Diseases,
Harvard
Medical
School
Brigham
Women's
Hospital,
Boston,
Massachusetts
02115
Correspondence:
lmucke{at}gladstone.ucsf.edu,
dselkoe{at}rics.bwh.harvard.edu
Cold Spring Harbor Perspectives in Medicine,
Год журнала:
2012,
Номер
2(3), С. a006312 - a006312
Опубликована: Янв. 10, 2012
Apolipoprotein
E
(APOE)
genotype
is
the
major
genetic
risk
factor
for
Alzheimer
disease
(AD);
ε4
allele
increases
and
ε2
protective.
In
central
nervous
system
(CNS),
apoE
produced
by
glial
cells,
present
in
high-density-like
lipoproteins,
interacts
with
several
receptors
that
are
members
of
low-density
lipoprotein
receptor
(LDLR)
family,
a
protein
binds
to
amyloid-β
(Aβ)
peptide.
There
variety
mechanisms
which
isoform
may
influence
AD.
substantial
evidence
differential
effects
on
AD
influenced
ability
affect
Aβ
aggregation
clearance
brain.
Other
also
likely
play
role
CNS
function
as
well
AD,
including
synaptic
plasticity,
cell
signaling,
lipid
transport
metabolism,
neuroinflammation.
ApoE
receptors,
LDLRs,
Apoer2,
very
(VLDLRs),
receptor-related
1
(LRP1)
appear
both
metabolism
toxicity.
Therapeutic
strategies
based
include
influencing
apoE/Aβ
interactions,
structure,
lipidation,
LDLR
family
member
function,
signaling.
Understanding
normal
disease-related
biology
connecting
apoE,
provide
novel
insights
into
pathogenesis
treatment.
