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Identification of a CD44-dependent control of astrocytic autophagic activity in Alzheimer's disease.

Overview

Authors: Haiyan Wang1,2, Ying Long3, Yu Tang4,5, Lijie Duan6, Zijie Wang1,2, Shuzhen Zhang3, Yanqing Yin3, Jiawei Zhou3, Wenjuan Wu5, Chunjiu Zhong1,2,7
ORCID iDs: Haiyan Wang
  1. Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China
  2. State Key Laboratory of Brain Function and Disorders, Institutes of Brain Science, Fudan University, Shanghai, China
  3. Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
  4. China Resources WITest (Shanghai) Medical Instruments Co., Ltd, Shanghai, China
  5. Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
  6. Department of Neurology, Jinshan Hospital Affiliated to Fudan University, Shanghai, China
  7. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
Institutions: Shanghai Medical College of Fudan University (China); Fudan University (China); Zhongshan Hospital (China); Chinese Academy of Sciences (China); Center for Excellence in Brain Science and Intelligence Technology (China); State Key Laboratory of Neuroscience; Tongji University (China); Shanghai East Hospital (China); Jinshan Hospital of Fudan University (China); Huashan Hospital (China)
Journal: The journal of prevention of Alzheimer's disease, volume 13, issue 8, article 100601
Dates: received 7 February 2026; accepted 8 May 2026; published online 20 May 2026; in print October 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.tjpad.2026.100601 · PMID 42160959 · PMCID PMC13199780 · OpenAlex W7161802554
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Machine learning, Evoked potentials, Connectivity
Keywords: Alzheimer's disease, CD44, Astrocytes, Autophagy, Transcriptomic
MeSH: Alzheimer Disease*, Astrocytes*, Autophagy*, Hyaluronan Receptors*, Animals, Brain, Humans, Up-Regulation (* major topic)
Topic: Autophagy in Disease and Therapy (Epidemiology, Medicine), according to OpenAlex
Funding: National Natural Science Foundation of China (82171408, 82472327); Shanghai Municipal Science and Technology Major Project, and the Health Commission of Jinshan District, Shanghai (JSKJ-KTQN-2022-05)
Citations: not cited yet (Europe PMC); 68 references in the paper

Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory impairment. Despite extensive research, the precise molecular mechanisms driving AD pathogenesis remain incompletely understood. This study sought to identify robust molecular targets and cellular basis underlying AD progression.

Methods: We performed a systematic analysis of cross-regional transcriptomic datasets from AD patients, integrating differential expression analysis across 14 Gene Expression Omnibus (GEO) datasets with cross-regional intersection mapping. Single-nucleus RNA sequencing (snRNA-seq) was employed to resolve cell-type-specific expression patterns. Furthermore, cellular communication analysis and functional enrichment of astrocyte-specific genes were conducted. The biological role of the identified candidate was validated in vitro using Aβ42 oligomer-treated primary astrocytes via siRNA-mediated knockdown and plasmid-driven overexpression, with autophagic activity assessed through LC3-II and p62 expression.

Results: The transmembrane glycoprotein receptor CD44 was identified as consistently upregulated across AD-vulnerable brain regions, including the temporal cortex, frontal cortex, entorhinal cortex, and hippocampus. snRNA-seq analysis identified this upregulation primarily to astrocytes. Intercellular signaling analysis indicated that the CD44-SPP1 axis enhanced astrocyte-glial crosstalk. Functional enrichment analysis linked astrocytic CD44 to the modulation of autophagy pathways. In vitro experiments demonstrated that CD44 knockdown promoted autophagic activation (increased LC3-II and decreased p62), whereas CD44 overexpression suppressed autophagic activity.

Conclusion: Our findings establish CD44 as a pivotal regulator of astrocytic autophagy in AD, highlighting its potential as a novel therapeutic target.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data availability

The datasets and custom code generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Authors: added Haiyan Wang (0000-0003-4177-6633); removed Haiyan Wang

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 5 keywords, 8 MeSH terms, 2 funders, 67 references.

Cite

This paper

Wang, H., Long, Y., Tang, Y., Duan, L., Wang, Z., Zhang, S., Yin, Y., Zhou, J., Wu, W., & Zhong, C. (2026). Identification of a CD44-dependent control of astrocytic autophagic activity in Alzheimer's disease. The journal of prevention of Alzheimer's disease, 13(8), 100601. https://doi.org/10.1016/j.tjpad.2026.100601

BibTeX

@article{wang2026identification,
author = {Wang, Haiyan and Long, Ying and Tang, Yu and Duan, Lijie and Wang, Zijie and Zhang, Shuzhen and Yin, Yanqing and Zhou, Jiawei and Wu, Wenjuan and Zhong, Chunjiu},
title = {{Identification of a CD44-dependent control of astrocytic autophagic activity in Alzheimer's disease}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2026},
month = may,
volume = {13},
number = {8},
pages = {100601},
publisher = {Elsevier},
issn = {2274-5807},
doi = {10.1016/j.tjpad.2026.100601},
url = {https://doi.org/10.1016/j.tjpad.2026.100601},
pmid = {42160959},
pmcid = {PMC13199780}
}

RIS

TY - JOUR
AU - Wang, Haiyan
AU - Long, Ying
AU - Tang, Yu
AU - Duan, Lijie
AU - Wang, Zijie
AU - Zhang, Shuzhen
AU - Yin, Yanqing
AU - Zhou, Jiawei
AU - Wu, Wenjuan
AU - Zhong, Chunjiu
TI - Identification of a CD44-dependent control of astrocytic autophagic activity in Alzheimer's disease
T2 - The journal of prevention of Alzheimer's disease
J2 - J Prev Alzheimers Dis
PY - 2026
DA - 2026/05/20
VL - 13
IS - 8
SP - 100601
SN - 2274-5807
PB - Elsevier
DO - 10.1016/j.tjpad.2026.100601
UR - https://doi.org/10.1016/j.tjpad.2026.100601
LA - en
ER -

CSL-JSON

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