Evidence map›Paper›PMID 38711159›Full record

ArticleAlzheimer's research & therapy2024

Selective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer's disease mouse model.

Caden M Henningfield, Neelakshi Soni, Ryan W Lee, Rishi Sharma, Jeffrey L Cleland, Kim N Green

Abstract read
In one paragraph

Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Native PLGA nanoparticles attenuate disease pathology via multiple pathways in 5xFAD Alzheimer's model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  2. Review
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  10. Clinical Radiosynthesis and Translation of [ACS chemical neuroscience · 2023
    Article
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.

Caden M HenningfieldDepartment of Neurobiology and Behavior, University of California, 3208 Biological Sciences III, Irvine, CA, 92697, USA.
Neelakshi SoniDepartment of Neurobiology and Behavior, University of California, 3208 Biological Sciences III, Irvine, CA, 92697, USA.
Ryan W LeeDepartment of Neurobiology and Behavior, University of California, 3208 Biological Sciences III, Irvine, CA, 92697, USA.
Rishi SharmaAshvattha Therapeutics, Inc, Redwood City, CA, 94065, USA.
Jeffrey L ClelandAshvattha Therapeutics, Inc, Redwood City, CA, 94065, USA.
Kim N GreenDepartment of Neurobiology and Behavior, University of California, 3208 Biological Sciences III, Irvine, CA, 92697, USA. kngreen@uci.edu.

Funding

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
Selective targeting and treatment of plaque associated microglia in a mouse model of Alzheimer’s DiseaseF31AG072852 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI HENNINGFIELD, CADEN MICHAEL · 2021 to 2023
$127k
NIA NIH HHS F31 AG072852NIA NIH HHS F31AG072852NIA NIH HHS R01AG056768NIA NIH HHS RF1 AG056768NINDS NIH HHS R01 NS083801NINDS NIH HHS R01NS083801
6 · The paper itself

Abstract

backgroundIn Alzheimer's disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease. Identifying approaches to specifically target plaque-associated microglia (PAMs) without interfering in the homeostatic functions of non-plaque associated microglia would afford a powerful tool and potential therapeutic avenue.

methodsHere, we demonstrated that a systemically administered nanomedicine, hydroxyl dendrimers (HDs), can cross the blood brain barrier and are preferentially taken up by PAMs in a mouse model of AD. As proof of principle, to demonstrate biological effects in PAM function, we treated the 5xFAD mouse model of amyloidosis for 4 weeks via systemic administration (ip, 2x weekly) of HDs conjugated to a colony stimulating factor-1 receptor (CSF1R) inhibitor (D-45113).

resultsTreatment resulted in significant reductions in amyloid-beta (Aβ) and a stark reduction in the number of microglia and microglia-plaque association in the subiculum and somatosensory cortex, as well as a downregulation in microglial, inflammatory, and synaptic gene expression compared to vehicle treated 5xFAD mice.

conclusionsThis study demonstrates that systemic administration of a dendranib may be utilized to target and modulate PAMs.

Indexed as

Alzheimer DiseaseDendrimersDisease Models, AnimalMice, TransgenicMicrogliaPlaque, AmyloidAmyloid beta-PeptidesAnimalsHumansMiceReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAmyloid beta-PeptidesCsf1r protein, mouseDendrimersReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAlzheimer’s diseaseAmyloidDendrimersInflammationMicroglia

Identifiers

PMID38711159
PMCPMC11071231

What OpenQuestion holds

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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.