Annals of Neurology,
Journal Year:
2024,
Volume and Issue:
95(4), P. 625 - 634
Published: Jan. 5, 2024
Alzheimer's
disease
(AD)
is
the
most
common
neurodegenerative
disorder
and
one
of
leading
causes
disability
worldwide.
The
apolipoprotein
E4
gene
(APOE4)
strongest
genetic
risk
factor
for
AD.
In
2023,
APOE4
National
Institute
on
Aging/Alzheimer's
Disease
Sequencing
Project
working
group
came
together
to
gather
data
discuss
question
whether
reduce
or
increase
as
a
therapeutic
intervention
It
was
unanimous
consensus
that
cumulative
from
multiple
studies
in
humans
animal
models
support
lowering
should
be
target
approaches
carriers.
ANN
NEUROL
2024;95:625-634.
Nature,
Journal Year:
2024,
Volume and Issue:
631(8022), P. 913 - 919
Published: July 10, 2024
Abstract
A
defining
pathological
feature
of
most
neurodegenerative
diseases
is
the
assembly
proteins
into
amyloid
that
form
disease-specific
structures
1
.
In
Alzheimer’s
disease,
this
characterized
by
deposition
β-amyloid
and
tau
with
conformations.
The
in
situ
structure
human
brain
unknown.
Here,
using
cryo-fluorescence
microscopy-targeted
cryo-sectioning,
cryo-focused
ion
beam-scanning
electron
microscopy
lift-out
cryo-electron
tomography,
we
determined
in-tissue
architectures
pathology
a
postmortem
disease
donor
brain.
plaques
contained
mixture
fibrils,
some
which
were
branched,
protofilaments,
arranged
parallel
arrays
lattice-like
structures.
Extracellular
vesicles
cuboidal
particles
defined
non-amyloid
constituents
plaques.
By
contrast,
inclusions
formed
clusters
unbranched
filaments.
Subtomogram
averaging
cluster
136
filaments
single
tomogram
revealed
polypeptide
backbone
conformation
filament
polarity
orientation
paired
helical
within
tissue.
Filaments
similar
to
each
other,
but
different
between
clusters,
showing
heterogeneity
spatially
organized
subcellular
location.
structural
approaches
outlined
here
for
tissues
have
applications
broad
range
diseases.
Alzheimer s & Dementia,
Journal Year:
2024,
Volume and Issue:
20(6), P. 4212 - 4233
Published: May 16, 2024
Compromised
autophagy,
including
impaired
mitophagy
and
lysosomal
function,
plays
pivotal
roles
in
Alzheimer's
disease
(AD).
Urolithin
A
(UA)
is
a
gut
microbial
metabolite
of
ellagic
acid
that
stimulates
mitophagy.
The
effects
UA's
long-term
treatment
AD
mechanisms
action
are
unknown.
Neuron,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 1, 2024
Autophagy
is
a
conserved
mechanism
that
degrades
damaged
or
superfluous
cellular
contents
and
enables
nutrient
recycling
under
starvation
conditions.
Many
neurodegeneration-associated
proteins
are
autophagy
substrates,
upregulation
ameliorates
disease
in
many
animal
models
of
neurodegeneration
by
enhancing
the
clearance
toxic
proteins,
proinflammatory
molecules,
dysfunctional
organelles.
inhibition
also
induces
neuronal
glial
senescence,
phenomenon
occurs
with
increasing
age
non-diseased
brains
as
well
response
to
stresses.
However,
aging
mutations
impair
autophagy.
This
creates
potentially
detrimental
feedback
loop
whereby
accumulation
these
disease-associated
impairs
their
autophagic
clearance,
facilitating
further
aggregation.
Thus,
understanding
how
interacts
aging,
neurodegenerative
diseases
temporal,
cellular,
genetic
context
important
for
future
clinical
application
autophagy-modulating
therapies
neurodegeneration.
Annals of Neurology,
Journal Year:
2024,
Volume and Issue:
95(4), P. 625 - 634
Published: Jan. 5, 2024
Alzheimer's
disease
(AD)
is
the
most
common
neurodegenerative
disorder
and
one
of
leading
causes
disability
worldwide.
The
apolipoprotein
E4
gene
(APOE4)
strongest
genetic
risk
factor
for
AD.
In
2023,
APOE4
National
Institute
on
Aging/Alzheimer's
Disease
Sequencing
Project
working
group
came
together
to
gather
data
discuss
question
whether
reduce
or
increase
as
a
therapeutic
intervention
It
was
unanimous
consensus
that
cumulative
from
multiple
studies
in
humans
animal
models
support
lowering
should
be
target
approaches
carriers.
ANN
NEUROL
2024;95:625-634.
