Evidence map›Paper›PMID 39764045›Full record

ArticlebioRxiv : the preprint server for biology2024

Comparative mapping of single-cell transcriptomic landscapes in neurodegenerative diseases.

E Keats Shwab, Zhaohui Man, Daniel C Gingerich, Julia Gamache, Melanie E Garrett, Geidy E Serrano, Thomas G Beach, Gregory E Crawford, Allison E Ashley-Koch, Ornit Chiba-Falek

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

E Keats ShwabDivision of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, 27710, USA.
Zhaohui ManDivision of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, 27710, USA.
Daniel C GingerichDivision of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, 27710, USA.
Julia GamacheDivision of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, 27710, USA.ORCID 0000-0002-3750-147X
Melanie E GarrettDuke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, 27701, USA.
Geidy E SerranoBanner Sun Health Research Institute, Sun City, Arizona, 85351, USA.
Thomas G BeachBanner Sun Health Research Institute, Sun City, Arizona, 85351, USA.
Gregory E CrawfordCenter for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, 27708, USA.
Allison E Ashley-KochDuke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, 27701, USA.
Ornit Chiba-FalekDivision of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, 27710, USA.

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI ALIREZA ATRI · 2021 to 2026
$24.9M
NEUROPATHOLOGY COREP30AG028377 · NIA · DUKE UNIVERSITY · PI WELSH-BOHMER, KATHLEEN ANNE · 2006 to 2011
$9.6M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
Lewy body neuropathologies and SNCA gene: variants expression and splicingRF1NS113548 · NINDS · DUKE UNIVERSITY · PI CHIBA-FALEK, ORNIT · 2020 to 2020
$3.8M
Deciphering the regulation of gene expression in the etiology of LOADR01AG057522 · NIA · DUKE UNIVERSITY · PI CHIBA-FALEK, ORNIT, LUTZ, MICHAEL WILLIAM · 2017 to 2021
$3.6M
Untangling the diversity in the genetic architecture of late-onset Alzheimer's disease using single cell multi-omicsRF1AG077695 · NIA · DUKE UNIVERSITY · PI CHIBA-FALEK, ORNIT · 2022 to 2022
$2.3M
NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG028377NIA NIH HHS P30 AG072980NIA NIH HHS R01 AG057522NIA NIH HHS RF1 AG077695NINDS NIH HHS RF1 NS113548NINDS NIH HHS U24 NS072026
6 · The paper itself

Abstract

introductionAlzheimer's disease (AD), Dementia with Lewy bodies (DLB), and Parkinson's disease (PD) represent a spectrum of neurodegenerative disorders (NDDs). Here, we performed the first direct comparison of their transcriptomic landscapes.

methodsWe profiled the whole transcriptomes of NDD cortical tissue by snRNA-seq. We used computational analyses to identify common and distinct differentially expressed genes (DEGs), biological pathways, vulnerable and disease-driver cell subtypes, and alteration in cell-to-cell interactions.

resultsThe same vulnerable inhibitory neuron subtype was depleted in both AD and DLB. Potentially disease-driving neuronal cell subtypes were present in both PD and DLB. Cell-cell communication was predicted to be increased in AD but decreased in DLB and PD. DEGs were most commonly shared across NDDs within inhibitory neuron subtypes. Overall, we observed the greatest transcriptomic divergence between AD and PD, while DLB exhibited an intermediate transcriptomic signature. DISCUSSION: These results help explain the clinicopathological spectrum of this group of NDDs and provide unique insights into the shared and distinct molecular mechanisms underlying the pathogenesis of NDDs.

Indexed as

Alzheimer’s diseasecell communicationcomparativedementia with Lewy bodiesParkinson’s diseasesingle-nucleus (sn)RNA-seqsynucleopathiestranscriptomicsvulnerable cell types

Identifiers

PMID39764045
PMCPMC11702568

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.