Nature,
Journal Year:
2024,
Volume and Issue:
628(8006), P. 154 - 161
Published: March 13, 2024
Abstract
Several
genetic
risk
factors
for
Alzheimer’s
disease
implicate
genes
involved
in
lipid
metabolism
and
many
of
these
are
highly
expressed
glial
cells
1
.
However,
the
relationship
between
glia
pathology
remains
poorly
understood.
Through
single-nucleus
RNA
sequencing
brain
tissue
disease,
we
have
identified
a
microglial
state
defined
by
expression
droplet-associated
enzyme
ACSL1
with
ACSL1-positive
microglia
being
most
abundant
patients
having
APOE4/4
genotype.
In
human
induced
pluripotent
stem
cell-derived
microglia,
fibrillar
Aβ
induces
expression,
triglyceride
synthesis
droplet
accumulation
an
APOE-dependent
manner.
Additionally,
conditioned
media
from
droplet-containing
lead
to
Tau
phosphorylation
neurotoxicity
Our
findings
suggest
link
neurotoxic
microglia-derived
factors,
potentially
providing
therapeutic
strategies
disease.
Cell Reports,
Journal Year:
2020,
Volume and Issue:
31(13), P. 107843 - 107843
Published: June 1, 2020
Damage-associated
microglia
(DAM)
profiles
observed
in
Alzheimer's
disease
(AD)-related
mouse
models
reflect
an
activation
state
that
could
modulate
AD
risk
or
progression.
To
learn
whether
human
(HAM)
display
a
similar
profile,
we
develop
method
for
purifying
cell
types
from
frozen
cerebrocortical
tissues
RNA-seq
analysis,
allowing
better
transcriptome
coverage
than
typical
single-nucleus
approaches.
The
HAM
profile
observe
bears
little
resemblance
to
the
DAM
profile.
Instead,
enhanced
aging
addition
other
disease-related
changes
such
as
APOE
upregulation.
Analyses
of
whole-tissue
and
single-cell/nucleus
datasets
corroborate
our
findings
suggest
lack
response
occurs
specifically
tissues,
not
neurodegenerative
settings.
These
results,
which
can
be
browsed
at
http://research-pub.gene.com/BrainMyeloidLandscape,
provide
genome-wide
picture
microglial
highlight
considerable
differences
between
disease.
Science,
Journal Year:
2020,
Volume and Issue:
370(6512), P. 66 - 69
Published: Oct. 2, 2020
Dementia
is
a
rapidly
rising
global
health
crisis
that
silently
disables
families
and
ends
lives
livelihoods
around
the
world.
To
date,
however,
no
early
biomarkers
or
effective
therapies
exist.
It
now
clear
brain
microglia
are
more
than
mere
bystanders
amyloid
phagocytes;
they
can
act
as
governors
of
neuronal
function
homeostasis
in
adult
brain.
Here,
we
highlight
fundamental
role
tissue-resident
macrophages
health.
Then,
suggest
how
chronic
impairment
microglia-neuron
cross-talk
may
secure
permanence
failure
synaptic
Alzheimer's
Parkinson's
diseases.
Understanding
to
assess
modulate
interactions
critical
for
will
be
key
developing
dementia.
Circulation Research,
Journal Year:
2020,
Volume and Issue:
127(3), P. 402 - 426
Published: July 16, 2020
The
diverse
leukocyte
infiltrate
in
atherosclerotic
mouse
aortas
was
recently
analyzed
9
single-cell
RNA
sequencing
and
2
mass
cytometry
studies.
In
a
comprehensive
meta-analysis,
we
confirm
4
known
macrophage
subsets-resident,
inflammatory,
interferon-inducible
cell,
Trem2
(triggering
receptor
expressed
on
myeloid
cells-2)
foamy
macrophages-and
identify
new
subset
resembling
cavity
macrophages.
We
also
find
that
monocytes,
neutrophils,
dendritic
cells,
natural
killer
innate
lymphoid
cells-2,
CD
(cluster
of
differentiation)-8
T
cells
form
prominent
separate
immune
cell
populations
aortas.
Many
CD4
express
IL
(interleukin)-17
the
chemokine
CXCR
(C-X-C
receptor)-6.
A
small
number
regulatory
helper
1
is
identified.
Immature
naive
are
present
both
healthy
Our
meta-analysis
overcomes
limitations
individual
studies
that,
because
their
experimental
approach,
over-
or
underrepresent
certain
populations.
Mass
demonstrate
surface
phenotype
provides
valuable
information
beyond
transcriptomes.
analysis
helps
resolve
some
long-standing
controversies
field.
First,
Acta Neuropathologica,
Journal Year:
2020,
Volume and Issue:
140(4), P. 513 - 534
Published: Aug. 9, 2020
Abstract
Multiple
sclerosis
(MS)
is
an
inflammatory,
demyelinating,
and
neurodegenerative
disease
of
the
central
nervous
system
(CNS)
triggered
by
autoimmune
mechanisms.
Microglia
are
critical
for
clearance
myelin
debris
in
areas
demyelination,
a
key
step
to
allow
remyelination.
TREM2
expressed
microglia
promotes
microglial
survival,
proliferation,
phagocytic
activity.
Herein
we
demonstrate
that
was
highly
on
myelin-laden
phagocytes
active
demyelinating
lesions
CNS
subjects
with
MS.
In
gene
expression
studies,
macrophages
from
genetic
deficiency
displayed
defect
pathways.
Treatment
new
agonistic
antibody
promoted
cuprizone
model
demyelination.
Effects
included
enhancement
uptake
degradation,
resulting
accelerated
removal
microglia.
Most
importantly,
antibody-dependent
activation
increased
density
oligodendrocyte
precursors
as
well
formation
mature
oligodendrocytes
thus
enhancing
remyelination
axonal
integrity.
These
results
relevant
they
propose
potential
target
promote
