Evidence map›Paper›PMID 22945846›Full record

ArticleJournal of molecular neuroscience : MN2013

Muscle-directed anti-Aβ single-chain antibody delivery via AAV1 reduces cerebral Aβ load in an Alzheimer's disease mouse model.

Junling Yang, Abhinandan Pattanayak, Min Song, Jinghong Kou, Hiroaki Taguchi, Sudhir Paul, Selvarangan Ponnazhagan, Robert Lalonde, Ken-ichiro Fukuchi

Abstract read
In one paragraph

Article in Journal of molecular neuroscience : MN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Muscle-Brain crosstalk in cognitive impairment.Frontiers in aging neuroscience · 2023
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  8. Immunotherapies for Aging-Related Neurodegenerative Diseases-Emerging Perspectives and New Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020
    Review
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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

9 authors at 5 institutions in 2 countries.

Junling YangDepartment of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, P.O. Box 1649, Peoria, IL, 61656, USA.
Abhinandan Pattanayak
Min Song
Jinghong Kou
Hiroaki Taguchi
Sudhir Paul
Selvarangan Ponnazhagan
Robert Lalonde
Ken-ichiro Fukuchi
University of Illinois Urbana-Champaign · USIllinois College · USThe University of Texas Health Science Center at Houston · USUniversité de Rouen Normandie · FRUniversity of Alabama at Birmingham · US

Funding

Innate immunity in Alzheimer's disease: Role of toll-like receptor signalingR01AG030399 · NIA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI FUKUCHI, KEN-ICHIRO · 2009 to 2013
$1.5M
Therapeutic delivery of single chain antibody for Alzheimer's diseaseR21EY018478 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI FUKUCHI, KEN-ICHIRO · 2007 to 2008
$427k
Catalytic and non-catalytic Ig gene delivery for Alzheimer's diseaseR21AG037814 · NIA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI FUKUCHI, KEN-ICHIRO · 2010 to 2011
$359k
AAV-mediated muscle-directed gene transfer for Alzheimer's diseaseR21AG029818 · NIA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI FUKUCHI, KEN-ICHIRO · 2007 to 2008
$358k
NEI NIH HHS EY018478NEI NIH HHS R21 EY018478NIA NIH HHS AG029818NIA NIH HHS AG030399NIA NIH HHS AG037814NIA NIH HHS R01 AG030399NIA NIH HHS R21 AG029818NIA NIH HHS R21 AG037814
6 · The paper itself

Abstract

We previously reported that anti-amyloid-beta (Aβ) single-chain antibody (scFv59) brain delivery via recombinant adeno-associated virus (rAAV) was effective in reducing cerebral Aβ load in an Alzheimer's disease (AD) mouse model without inducing inflammation. Here, we investigated the prophylactic effects and mechanism of a muscle-directed gene therapy modality in an AD mouse model. We injected rAAV serotype 1 encoding scFv59 into the right thigh muscles of 3-month-old mice. Nine months later, high levels of scFv59 expression were confirmed in the thigh muscles by both immunoblotting and immunohistochemistry. As controls, model mice were similarly injected with rAAV1 encoding antihuman immunodeficiency virus Gag antibody (scFvGag). AAV1-mediated scFv59 gene delivery was effective in decreasing Aβ deposits in the brain. Compared with the scFvGag group, levels of Aβ in cerebrospinal fluid (CSF) decreased significantly while Aβ in serum tended to increase in the scFv59 group. AAV1-mediated scFv59 gene delivery may alter the equilibrium of Aβ between the blood and brain, resulting in an increased efflux of Aβ from the brain owing to antibody-mediated sequestration/clearance of peripheral Aβ. Our results suggest that muscle-directed scFv59 delivery via rAAV1 may be a prophylactic option for AD and that levels of CSF Aβ may be used to evaluate the efficacy of anti-Aβ immunotherapy.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainDependovirusDisease Models, AnimalGene ExpressionGene TargetingGenetic TherapyImmunization, PassiveMiceMice, Inbred C57BLMusclesSingle-Chain AntibodiesAmyloid beta-PeptidesSingle-Chain Antibodies

Identifiers

PMID22945846
PMCPMC3545079
OpenAlexW2032044611

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.