Evidence map›Paper›PMID 41256571›Full record

ArticlebioRxiv : the preprint server for biology2025

Brain Region-Specific Epigenomic Reorganization and Altered Cell States in Alzheimer's Disease.

Wenliang Wang, Peter Berube, Bing Yang, Rosa Castanon, Anna Bartlett, Kaushik Komandur, Joseph R Nery, Cesar Barragan, Mia Kenworthy, Cynthia Valadon and 17 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Wenliang WangGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Peter BerubeGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Bing YangDepartment of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Rosa CastanonGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Anna BartlettGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Kaushik KomandurGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Joseph R NeryGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Cesar BarraganGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Mia KenworthyGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Cynthia ValadonGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Jordan AltshulGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Alaina PetrellaGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Derek ChanGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Chumo ChenGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Andrea Saldaña AcerboGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Jammy LuoGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Manya JainGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Eshaan SomaGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Huaming ChenGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Michelle LiemFlow Cytometry Core Facility, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Mikayla MarrinFlow Cytometry Core Facility, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Caz O'ConnorFlow Cytometry Core Facility, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.
Nathan ZemkeDepartment of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Derek OakleyDepartment of Pathology, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA, USA.
Bing RenNew York Genome Center, New York, NY 10013, USA.
Bradley T HymanHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-7959-9401
Joseph R EckerGenomic Analysis Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.

Funding

Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
Multi-omic Brain Cell Atlas of Alzheimer's Disease ProgressionR56AG069107 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HYMAN, BRADLEY T., REN, BING · 2020 to 2020
$1.9M
NIA NIH HHS P30 AG062421NIA NIH HHS R56 AG069107
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder, yet the molecular mechanisms underlying its region- and cell-type-specific pathogenesis remain poorly defined. Here, we generated a large-scale, single-cell multi-omic atlas-integrating DNA methylation and 3D genome architecture-from postmortem brain tissue of matched AD patients and cognitively normal controls. Samples were collected from three brain regions with distinct vulnerability to AD pathology: the temporal cortex (TC), primary visual cortex (VC), and prefrontal cortex (PFC). Our dataset comprises over 230,000 individual cells, spanning major neuronal and glial populations, and provides a high-resolution view of multi-layer epigenomic regulation. We identified widespread AD-associated DNA methylation changes and marked reorganization of 3D genome structure, including alterations in A/B compartments, topologically associating domains (TADs), and chromatin loops. These changes are strongly region-specific: TC displays pronounced hypermethylation, transcriptional downregulation, and elevated boundary density, whereas VC shows opposing trends and PFC an intermediate profile. We further uncovered previously unrecognized AD-associated glial and neuronal states defined by coordinated epigenomic dysregulation and recurrent genomic deletions, particularly near telomeric regions. This region-resolved, single-cell multi-omic atlas reveals divergent epigenomic trajectories across brain regions and cell types in AD, offering new mechanistic insights and a framework for targeted therapeutic strategies.

Identifiers

PMID41256571
PMCPMC12621709

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Registered trials

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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.