Evidence map›Paper›PMID 42050212›Full record

ReviewMolecular neurobiology2026

CD33 Isoform Splicing Dysregulation: A Molecular Determinant of Microglial Dysfunction in Alzheimer's Disease Pathology.

Xiao-Yan Li, Yu Zhang, Zhao Ran, Jia-Xin Luo, Xiao-Qin Yu, Mei-Hong Lu

Abstract readReview
PubMed Publisher
In one paragraph

Review in Molecular neurobiology, 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

6 authors.

Xiao-Yan LiChongqing Key Laboratory of Sichuan-Chongqing Co-Construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Yu ZhangHealth Management Center, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
Zhao RanChongqing Key Laboratory of Sichuan-Chongqing Co-Construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Jia-Xin LuoChongqing Key Laboratory of Sichuan-Chongqing Co-Construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Xiao-Qin YuChongqing Key Laboratory of Sichuan-Chongqing Co-Construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Mei-Hong LuChongqing Key Laboratory of Sichuan-Chongqing Co-Construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China. lmh0929@cdutcm.edu.cn.

Funding

Sichuan Provincial Administration of Traditional Chinese Medicine Grant No. 25MSZX550Sichuan Science and Technology Program Grant No. 2025ZNSFSC1799
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, and chronic neuroinflammation. Genome-wide association studies (GWAS) have identified microglial dysfunction as central to AD pathogenesis, with CD33 emerging as a critical genetic risk factor. This review explores the dual roles of CD33 isoforms, CD33M (pro-pathogenic) and CD33m (protective), in modulating microglial activity, Aβ clearance, and neuroinflammatory responses. We dissect the molecular mechanisms underlying isoform formation, including genetic polymorphisms (e.g., rs3865444, rs12459419) and splicing regulation by hnRNPA/B, PTBP1, and SRSF1. Additionally, we highlight the antagonistic interplay between CD33 and TREM2, emphasizing their convergence on DAP12 signaling and downstream pathways. Emerging therapeutic strategies targeting CD33, such as isoform-specific immunotherapies, small-molecule splicing modulators, and Siglec-glycan interactions, are critically evaluated for their potential to mitigate AD pathology. By integrating recent preclinical and clinical advancements, this review underscores the necessity of precision approaches to harness CD33's therapeutic potential while addressing challenges like blood-brain barrier penetration and species-specific discrepancies.

Indexed as

Alternative SplicingAlzheimer DiseaseMicrogliaSialic Acid Binding Ig-like Lectin 3AnimalsHumansProtein IsoformsCD33 protein, humanProtein IsoformsSialic Acid Binding Ig-like Lectin 3Alzheimer’s diseaseCD33 isoformsMicrogliaTREM2

Identifiers

What Socratic 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 Socratic graph.