CD22 regulates Aβ clearance in microglia through INPP5D signaling.
Overview
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, The Army Medical University (Third Military Medical University), Chongqing, China
- Institute of Advanced Pathology Research, Jinfeng Laboratory, Chongqing, China
Abstract
Introduction: Impaired microglial clearance of amyloid-β (Aβ) is a central driver of Alzheimer's disease (AD), yet the mechanisms governing intracellular Aβ degradation remain poorly defined.
Methods: We investigated the role of CD22 in microglial Aβ processing using primary microglia, transcriptomic profiling, and hippocampal samples from AD patients and transgenic mice.
Results: We identified CD22 as an Aβ-inducible signaling regulator that restrains microglial Aβ processing. CD22 expression was elevated in the hippocampus of AD patients and transgenic mice and was rapidly induced by Aβ in microglia. Functionally, CD22 knockdown enhanced intracellular Aβ degradation without affecting initial uptake. Transcriptomic profiling identified the AD risk gene INPP5D as a key downstream effector of CD22. Loss of CD22 suppressed INPP5D expression and promoted AKT activation, while INPP5D overexpression partially rescued the enhanced Aβ clearance phenotype. These findings define a CD22-INPP5D signaling axis that acts as a molecular brake on microglial Aβ processing. Aβ itself induces CD22 expression, revealing a feed-forward inhibitory loop in which amyloid accumulation limits its own clearance.
Discussion: Collectively, these findings identify a regulatory mechanism controlling intracellular Aβ degradation and suggest the CD22-INPP5D axis as a potential therapeutic target for AD.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
Tracing map
A tracing map links a paper to the code its authors published: this paper has none, so it has no map.
Data
Data links
- ncbi.nlm.nih.gov/
geo , NCBI; found in the text, “Bioinformatics analysis”
Data availability statement
The datasets presented in this study can be found in online repositories. The names of the repository/
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 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 6 authors, 5 keywords, 2 funders, 24 references.
Cite
This paper
Zou, D.-Z., Li, J., Long, Q.-S., Zhang, R.-Q., Zhu, B.-L., & Tan, J.-Z. (2026). CD22 regulates Aβ clearance in microglia through INPP5D signaling. Frontiers in cellular neuroscience, 20, 1886995. https://
BibTeX
@article{zou2026cd22,
author = {Zou, De-Zhi and Li, Jun and Long, Qiu-Shuang and Zhang, Ruo-Qi and Zhu, Bing-Lin and Tan, Jia-Ze},
title = {{CD22 regulates Aβ clearance in microglia through INPP5D signaling}},
journal = {Frontiers in cellular neuroscience},
year = {2026},
month = jul,
volume = {20},
pages = {1886995},
publisher = {Frontiers Media SA},
issn = {1662-5102},
doi = {10.3389/
url = {https://
pmid = {42582107},
pmcid = {PMC13457040}
}
RIS
TY - JOUR
AU - Zou, De-Zhi
AU - Li, Jun
AU - Long, Qiu-Shuang
AU - Zhang, Ruo-Qi
AU - Zhu, Bing-Lin
AU - Tan, Jia-Ze
TI - CD22 regulates Aβ clearance in microglia through INPP5D signaling
T2 - Frontiers in cellular neuroscience
J2 - Front Cell Neurosci
PY - 2026
DA - 2026/
VL - 20
SP - 1886995
SN - 1662-5102
PB - Frontiers Media SA
DO - 10.3389/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.3389/
"type": "article-journal",
"title": "CD22 regulates Aβ clearance in microglia through INPP5D signaling",
"container-title": "Frontiers in cellular neuroscience",
"author": [
{
"family": "Zou",
"given": "De-Zhi"
},
{
"family": "Li",
"given": "Jun"
},
{
"family": "Long",
"given": "Qiu-Shuang"
},
{
"family": "Zhang",
"given": "Ruo-Qi"
},
{
"family": "Zhu",
"given": "Bing-Lin"
},
{
"family": "Tan",
"given": "Jia-Ze"
}
],
"container-title-short":
"volume": "20",
"page": "1886995",
"DOI": "10.3389/
"PMID": "42582107",
"PMCID": "PMC13457040",
"ISSN": "1662-5102",
"publisher": "Frontiers Media SA",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
7,
28
]
]
}
}
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.1002/alz.71471 [code]
- How does type 2 diabetes modify the risk of Alzheimer's disease?Journal: Alzheimer's & dementia : the journal of the Alzheimer's AssociationIn common: Alzheimer's / dementia, cellular / molecular, 3 references
- [2] doi:10.1016/j.celrep.2026.117235 [code]
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.Journal: Cell reportsIn common: Alzheimer's / dementia, cellular / molecular, 3 references
- [3] doi:10.1038/s41467-026-74037-5
- Microglial CD31 suppresses Aβ clearance and promotes Alzheimer pathology in 5×FAD mice.Journal: Nature communicationsIn common: Alzheimer's / dementia, mouse, cellular / molecular, 2 references
- [4] doi:10.1111/ejn.70480 [code]
- Astrocyte Proximity Protects Synapses From Human Amyloid-Beta Induced Degeneration in a Mouse Ex Vivo Model of Early Alzheimer's Disease.Journal: The European journal of neuroscienceIn common: Alzheimer's / dementia, mouse, cellular / molecular, 2 references
- [5] doi:10.1007/s00401-026-03036-z
- Mechanisms of increased Alzheimer's disease pathology with R47H and R62H TREM2 variants.Journal: Acta neuropathologicaIn common: Alzheimer's / dementia, cellular / molecular, 2 references
- [6] doi:10.1038/s41588-026-02722-8 [code]
- A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations.Journal: Nature geneticsIn common: Alzheimer's / dementia, cellular / molecular, 2 references
- [7] doi:10.1038/s44321-026-00488-4 [code]
- DeepPlaque: a scalable multimodal platform for Aβ pathology and cell analysis in Alzheimer's disease.Journal: EMBO molecular medicineIn common: Alzheimer's / dementia, cellular / molecular, 2 references
- [8] doi:10.1038/s41593-026-02267-3 [code]
- Spatial proteomic analysis in human Alzheimer's disease brains enables identification of microenvironment-depende
nt microglial cell states. Journal: Nature neuroscienceIn common: Alzheimer's / dementia, cellular / molecular, 2 references - [9] doi:10.1038/s41467-026-73003-5 [code]
- Gpnmb defines a phagocytic state of microglia linked to cell death in prion disease mouse model.Journal: Nature communicationsIn common: mouse, cellular / molecular, 2 references
- [10] doi:10.3389/fnagi.2026.1768436
- TAS2R38 taster variants-linked MGAM expression in Alzheimer's disease: a novel target for precision drug repurposing.Journal: Frontiers in aging neuroscienceIn common: Alzheimer's / dementia, cellular / molecular, 2 references
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.
Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.