Evidence map›Paper›PMID 42728785›Full record

ArticleClinical and translational medicine2026

Integrative analysis of single-cell multi-omics reveals heterogeneity in piriform cortex principal neurons and their selective vulnerability in Alzheimer's disease.

Jiayue Meng, Miaomiao Zhang, Yujie Chen, Mengyao Han, Nianhao Cheng, Ruifang Cao, Qinwen He, Yaya Zhao, Liyun Yuan, Guoqing Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2026. 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

10 authors.

Jiayue MengBio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID https://orcid.org/0009-0003-5744-063X
Miaomiao ZhangState Key Laboratory of Immune Response and Immunotherapy, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Yujie ChenBio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Mengyao HanBio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Nianhao ChengBio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Ruifang CaoBio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Qinwen HeBio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Yaya ZhaoState Key Laboratory of Immune Response and Immunotherapy, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Liyun YuanBio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Guoqing ZhangBio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID https://orcid.org/0000-0001-8827-7546

Funding

National Key R&D Program of China 2024YFA1307704National Key R&D Program of China 2025YFF0511500National Natural Science Foundation of China 82003361Youth Innovation Promotion Association of CAS, China YIPA2023291
6 · The paper itself

Abstract

backgroundThe piriform cortex (PIR) is a key region of the olfactory system and is increasingly implicated in Alzheimer's disease (AD). However, the cellular heterogeneity of principal neurons (PN) in this region and their selective vulnerability in AD remain poorly understood.

methodsHere, we integrated single-cell multi-omics datasets to systematically characterize PIR PN heterogeneity. We identified four transcriptionally and epigenetically distinct PN subtypes with different spatial distributions across the anterior and posterior PIR.

resultsIn AD mouse models, the abundance of the Reln-positive superficial-layer (Reln+ SL) subtype was spatially associated with amyloid-β pathology, and its reduced proportion was confirmed by multiplex immunofluorescence. Cross-region comparison revealed that Reln+ SL neurons shared a Gpc5-high/Sort1-low molecular signature with vulnerable layer II excitatory neurons in the entorhinal cortex (EC). In human AD, this vulnerability-associated signature showed progressive enrichment in EC layer II neurons across Braak stages I-III. Furthermore, A Sort1-containing co-expression module captured regional differences between lateral and medial EC layer II populations and was enriched for proteostasis-related pathways.

conclusionsThese findings reveal shared molecular features associated with selective vulnerability across PIR and EC layer II neurons and identify a proteostasis-related program linked to regional differences in neuronal vulnerability during AD. KEY POINTS: Single-cell multi-omics reveals molecular heterogeneity among piriform cortex principal neurons. Reln+ superficial-layer neurons show selective vulnerability in AD. Cross-region comparison identifies a shared Gpc5-high/Sort1-low signature in vulnerable layer II neurons of EC and PIR.

Indexed as

Alzheimer DiseaseNeuronsPiriform CortexSingle-Cell AnalysisAnimalsDisease Models, AnimalHumansMaleMiceMultiomicsAlzheimer's diseasemulti‐omicspiriform cortexprincipal neuronsselective vulnerabilitysingle‐cell RNA sequencing

Identifiers

PMID42728785
PMCPMC13570217

What OpenQuestion holds

Textmetadata
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.