Evidence map›Paper›PMID 31685865›Full record

ArticleScientific reports2019

Intra- and extracellular β-amyloid overexpression via adeno-associated virus-mediated gene transfer impairs memory and synaptic plasticity in the hippocampus.

Stefania Forner, Alessandra C Martini, G Aleph Prieto, Cindy T Dang, Carlos J Rodriguez-Ortiz, Jorge Mauricio Reyes-Ruiz, Laura Trujillo-Estrada, Celia da Cunha, Elizabeth J Andrews, Jimmy Phan and 12 more

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

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

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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

22 authors at 3 institutions in 2 countries.

Stefania FornerInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.ORCID http://orcid.org/0000-0001-7977-4866
Alessandra C MartiniInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.ORCID http://orcid.org/0000-0002-8447-6756
G Aleph PrietoInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Cindy T DangInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Carlos J Rodriguez-OrtizDepartment of Medicine, University of California, Irvine, Irvine, CA, 92697, USA.ORCID http://orcid.org/0000-0003-2688-947X
Jorge Mauricio Reyes-RuizDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA.
Laura Trujillo-EstradaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Celia da CunhaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Elizabeth J AndrewsInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Jimmy PhanInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Jordan Vu HaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Allissa V Z D ChangInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Yona LevitesDepartment of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.
Pedro E CruzDepartment of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.
Rahasson AgerInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Rodrigo MedeirosInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.ORCID http://orcid.org/0000-0002-9399-7852
Masashi KitazawaDepartment of Medicine, University of California, Irvine, Irvine, CA, 92697, USA.
Charles G GlabeDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA.
Carl W CotmanInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.
Todd GoldeDepartment of Neuroscience, University of Florida, Gainesville, FL, 32610, USA.
David Baglietto-VargasInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.ORCID http://orcid.org/0000-0003-1441-3175
Frank M LaFerlaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA. laferla@uci.edu.
University of California, Irvine · USUniversity of Florida · USThe University of Queensland · AU

Funding

TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI COTMAN, CARL WAYNE · 1985 to 2018
$24.8M
Integrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6M
Learning and Memory Impairments in Transgenic AD ModelsR01AG027544 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2007 to 2016
$3.1M
Gene Expression, Compensation Mechanisms, and Successful Cognitive AgingR01AG034667 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI COTMAN, CARL WAYNE · 2009 to 2013
$1.7M
A Novel Approach to Study Synaptic Plasticity in Isolated Synaptosomes using Flow CytometryR21AG048506 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI COTMAN, CARL WAYNE · 2015 to 2016
$425k
The impact of endocytic protein Tom1 on Alzheimer's diseaseR21AG054884 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2016 to 2017
$425k
HSRD VA QUE 16-170NIA NIH HHS P01 AG000538NIA NIH HHS R01 AG027544NIA NIH HHS R01 AG034667NIA NIH HHS R21 AG048506NIA NIH HHS R21 AG054884NIA NIH HHS U01 AG046139
6 · The paper itself

Abstract

Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is currently conceptualized as a disease of synaptic failure. Synaptic impairments are robust within the AD brain and better correlate with dementia severity when compared with other pathological features of the disease. Nevertheless, the series of events that promote synaptic failure still remain under debate, as potential triggers such as β-amyloid (Aβ) can vary in size, configuration and cellular location, challenging data interpretation in causation studies. Here we present data obtained using adeno-associated viral (AAV) constructs that drive the expression of oligomeric Aβ either intra or extracellularly. We observed that expression of Aβ in both cellular compartments affect learning and memory, reduce the number of synapses and the expression of synaptic-related proteins, and disrupt chemical long-term potentiation (cLTP). Together, these findings indicate that during the progression AD the early accumulation of Aβ inside neurons is sufficient to promote morphological and functional cellular toxicity, a phenomenon that can be exacerbated by the buildup of Aβ in the brain parenchyma. Moreover, our AAV constructs represent a valuable tool in the investigation of the pathological properties of Aβ oligomers both in vivo and in vitro.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsCells, CulturedDependovirusGenetic VectorsGene Transfer TechniquesHippocampusMaze LearningMemoryMiceMice, Inbred C57BLNeuronal PlasticityPeptide FragmentsSynapsesAmyloid beta-Peptidesamyloid beta-protein (1-42)Peptide Fragments

Identifiers

PMID31685865
PMCPMC6828807
OpenAlexW2988480825

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.