Genetic and multi-omic resources for Alzheimer disease and related dementia from the Knight Alzheimer Disease Research Center
Scientific Data,
Journal Year:
2024,
Volume and Issue:
11(1)
Published: July 12, 2024
Abstract
The
Knight-Alzheimer
Disease
Research
Center
(Knight-ADRC)
at
Washington
University
in
St.
Louis
has
pioneered
and
led
worldwide
seminal
studies
that
have
expanded
our
clinical,
social,
pathological,
molecular
understanding
of
Alzheimer
Disease.
Over
more
than
40
years,
research
volunteers
been
recruited
to
participate
cognitive,
neuropsychologic,
imaging,
fluid
biomarkers,
genomic
multi-omic
studies.
Tissue
longitudinal
data
collected
foster,
facilitate,
support
on
dementia
aging.
Genetics
high
throughput
-
omics
core
(GHTO)
26,000
biological
samples
from
6,625
Knight-ADRC
participants.
Samples
available
include
DNA,
RNA,
non-fasted
plasma,
cerebrospinal
pellets,
peripheral
blood
mononuclear
cells.
GHTO
performed
deep
profiling
(genomic,
transcriptomic,
epigenomic,
proteomic,
metabolomic)
large
number
brain
(n
=
2,117),
CSF
2,012)
blood/plasma
8,265)
with
the
goal
identifying
novel
risk
protective
variants,
identify
biomarkers
causal
druggable
targets.
Overall,
resources
increase
Language: Английский
Linking genomic and proteomic signatures to brain amyloid burden: insights from GR@ACE/DEGESCO
Functional & Integrative Genomics,
Journal Year:
2025,
Volume and Issue:
25(1)
Published: March 25, 2025
Alzheimer's
disease
(AD)
is
a
complex
with
strong
genetic
component,
yet
many
risk
factors
remain
unknown.
We
combined
genome-wide
association
studies
(GWAS)
on
amyloid
endophenotypes
measured
in
cerebrospinal
fluid
(CSF)
and
positron
emission
tomography
(PET)
as
surrogates
of
pathology,
which
may
provide
insights
into
the
underlying
biology
disease.
performed
meta-GWAS
CSF
Aβ42
PET
measures
combining
six
independent
cohorts
(n
=
2,076).
Given
opposite
beta
direction
Aβ
phenotypes
measures,
only
signals
showing
directions
were
considered
for
analysis
376,599).
explored
amyloidosis
signature
proteome
using
SOMAscan
proteomics
(ACE
cohort,
n
1,008),
connected
it
GWAS
loci
modulating
an
enrichment
overlapping
hits.
Finally,
we
compared
our
results
large
meta-analysis
publicly
available
datasets
13,409)
13,116).
After
filtering
meta-GWAS,
observed
significance
rs429358-APOE
locus
annotated
nine
suggestive
replicated
APOE
CSF-PET
identifying
multiple
AD-associated
genes
including
novel
GADL1
locus.
Additionally,
found
1,387
FDR-significant
proteins
associated
levels.
The
overlap
among
burden
was
minimal
35).
revealed
mechanisms
connecting
plasma
membrane's
anchored
synapse
physiology
mental
disorders
that
meta-analysis.
Combining
analyses
effectively
elucidate
causative
molecular
behind
mobilization
AD
physiopathology.
Language: Английский
Drug Repositioning Based on Cerebrospinal Fluid Proteomes Using Connectivity Map Framework
Methods in molecular biology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 323 - 332
Published: Jan. 1, 2025
Language: Английский
Connecting genomic and proteomic signatures of amyloid burden in the brain
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 6, 2024
Alzheimer's
disease
(AD)
has
a
high
heritable
component
characteristic
of
complex
diseases,
yet
many
the
genetic
risk
factors
remain
unknown.
We
combined
genome-wide
association
studies
(GWAS)
on
amyloid
endophenotypes
measured
in
cerebrospinal
fluid
(CSF)
and
positron
emission
tomography
(PET)
as
surrogates
pathology,
which
may
be
helpful
to
understand
underlying
biology
disease.
Language: Английский