Evidence map›Paper›PMID 32803224›Full record

ArticleHuman molecular genetics2020

Gene therapy for Alzheimer's disease targeting CD33 reduces amyloid beta accumulation and neuroinflammation.

Ana Griciuc, Anthony N Federico, Jeyashree Natasan, Angela M Forte, Danielle McGinty, Huong Nguyen, Adrienn Volak, Stanley LeRoy, Sheetal Gandhi, Eli P Lerner and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
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

72 citing papers in PubMed, 116 citations in OpenAlex.

  1. Review
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  9. Beyond Neuroinflammation: Microglia at the Crossroads of Amyloid, Tau, and Neurodegeneration in Alzheimer's Disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review
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  16. Article
  17. Immune modulation to treat Alzheimer's disease.Molecular neurodegeneration · 2025
    Review
  18. Article
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  20. Article

12 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 1 country.

Ana GriciucGenetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Anthony N FedericoGenetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Jeyashree NatasanMolecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02114, USA.
Angela M ForteGenetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Danielle McGintyGenetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Huong NguyenAlzheimer's Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Adrienn VolakMolecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02114, USA.
Stanley LeRoyMolecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02114, USA.
Sheetal GandhiAlzheimer's Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Eli P LernerAlzheimer's Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Eloise HudryAlzheimer's Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Rudolph E TanziGenetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Casey A MaguireMolecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02114, USA.
Harvard University · USMassachusetts General Hospital · US

Funding

Role of apolipoprotein E in age and amyloid beta related neuronal dysfunctionR00AG047336 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HUDRY, ELOISE · 2017 to 2019
$747k
CD33 and Alzheimer's Disease: from Biology to TherapyR00AG049056 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI GRICIUC, ANA · 2017 to 2019
$747k
NIA NIH HHS R00 AG047336NIA NIH HHS R00 AG049056
6 · The paper itself

Abstract

Neuroinflammation is a key contributor to the pathology of Alzheimer's disease (AD). CD33 (Siglec-3) is a transmembrane sialic acid-binding receptor on the surface of microglial cells. CD33 is upregulated on microglial cells from post-mortem AD patient brains, and high levels of CD33 inhibit uptake and clearance of amyloid beta (Aβ) in microglial cell cultures. Furthermore, knockout of CD33 reduces amyloid plaque burden in mouse models of AD. Here, we tested whether a gene therapy strategy to reduce CD33 on microglia in AD could decrease Aβ plaque load. Intracerebroventricular injection of an adeno-associated virus (AAV) vector-based system encoding an artificial microRNA targeting CD33 (miRCD33) into APP/PS1 mice reduced CD33 mRNA and TBS-soluble Aβ40 and Aβ42 levels in brain extracts. Treatment of APP/PS1 mice with miRCD33 vector at an early age (2 months) was more effective at reducing Aβ plaque burden than intervening at later times (8 months). Furthermore, early intervention downregulated several microglial receptor transcripts (e.g. CD11c, CD47 and CD36) and pro-inflammatory activation genes (e.g. Tlr4 and Il1b). Marked reductions in the chemokine Ccl2 and the pro-inflammatory cytokine Tnfα were observed at the protein level in the brain of APP/PS1 mice treated with miRCD33 vector. Overall, our data indicate that CD33 is a viable target for AAV-based knockdown strategies to reduce AD pathology. One Sentence Summary: A gene therapy approach for Alzheimer's disease using adeno-associated virus vector-based knockdown of CD33 reduced amyloid beta accumulation and neuroinflammation.

Indexed as

Genetic TherapyAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainDependovirusDisease Models, AnimalHumansMiceMice, TransgenicMicrogliaPlaque, AmyloidPresenilin-1Sialic Acid Binding Ig-like Lectin 3Amyloid beta-PeptidesAmyloid beta-Protein PrecursorCD33 protein, humanPresenilin-1Sialic Acid Binding Ig-like Lectin 3

Identifiers

PMID32803224
PMCPMC7566501
OpenAlexW3074486531

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.