Evidence map›Paper›PMID 40748756›Full record

ArticleCell reports2025

Aggrecan protects against plaque accumulation and is essential for proper microglial responses to plaques.

Rocio A Barahona, Nellie E Kwang, Aashna R Kono-Soosaipillai, Giovanna Rubio Salgado, Kristine M Tran, Yueh-Hao Lu, Siddharth Reddy, Celia da Cunha, Eric Velazquez-Rivera, Joshua D Crapser and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

13 authors.

Rocio A BarahonaDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA.
Nellie E KwangDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA.
Aashna R Kono-SoosaipillaiDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA.
Giovanna Rubio SalgadoDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA.
Kristine M TranDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA.
Yueh-Hao LuDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA.
Siddharth ReddyDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA.
Celia da CunhaDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA.
Eric Velazquez-RiveraDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Joshua D CrapserDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Xiangmin XuInstitute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, Irvine, CA 92697, USA; Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Lindsay A HohsfieldDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, Irvine, CA 92697, USA.
Kim N GreenDepartment of Neurobiology and Behavior, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, Irvine, CA 92697, USA. Electronic address: kngreen@uci.edu.

Funding

UC Irvine MODEL-ADU54AG054349 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Kim Green · 2017 to 2026
$71.9M
Origins, properties, and therapeutic potential of cells that repopulate the microglia-depleted adult brainR01NS083801 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Kim Green · 2014 to 2026
$5.6M
Microglia are necessary for cortical plaque formation in Alzheimer's diseaseRF1AG056768 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GREEN, KIM · 2018 to 2018
$2.7M
Role of Disease-Associated Microglia in Alzheimer's diseaseR01AG081599 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Kim Green · 2024 to 2026
$2.3M
Summer Medical student Aging and Alzheimer disease Research Training (SMAART) programT35AG076424 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Joshua Grill, Elizabeth Head · 2022 to 2026
$361k
Defining the role of perineuronal nets in Alzheimer's Disease pathologyF31AG082501 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BARAHONA, ROCIO ALEJANDRA · 2023 to 2024
$88k
NIA NIH HHS F31 AG082501NIA NIH HHS R01 AG081599NIA NIH HHS RF1 AG056768NIA NIH HHS T35 AG076424NIA NIH HHS U54 AG054349NINDS NIH HHS R01 NS083801
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid plaques and neurofibrillary tangles. Recent evidence implicates extracellular matrix (ECM) dysfunction in disease pathogenesis, including extensive loss of perineuronal nets (PNNs). PNNs are neuron-ensheathing condensed ECM structures composed of chondroitin sulfate proteoglycans, including the main constituent aggrecan (ACAN). To explore the role of PNNs in AD, we utilize the 5xFAD model and genetically target Acan in Nestin-expressing cells, resulting in loss of ACAN and ablation of the PNN structure. In 5xFAD mice, ACAN cKO results in increased plaque deposition, reduced plaque sphericity, and impaired microglia-plaque association. Single-cell spatial transcriptomics identifies an enhanced disease-associated microglia (DAM) phenotype in 5xFAD ACAN cKO mice, which is accompanied by decreased dystrophic neurite formation. Collectively, our data suggest that PNNs may play a crucial role in mediating the microglial response to plaques.

Indexed as

AggrecansAlzheimer DiseaseMicrogliaPlaque, AmyloidAnimalsDisease Models, AnimalExtracellular MatrixHumansMiceMice, KnockoutMice, TransgenicNestinAggrecansNestin5xFADaggrecanAlzheimer’s diseaseamyloid-betaCP: Cell biologyCP: Neuroscienceextracellular matrixmicroglianeurodegenerationperineuronal netsplaques

Identifiers

PMID40748756
PMCPMC12445281

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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.