Evidence map›Paper›PMID 32635578›Full record

ArticleCells2020

Astrocyte- and Neuron-Derived Extracellular Vesicles from Alzheimer's Disease Patients Effect Complement-Mediated Neurotoxicity.

Carlos J Nogueras-Ortiz, Vasiliki Mahairaki, Francheska Delgado-Peraza, Debamitra Das, Konstantinos Avgerinos, Erden Eren, Matthew Hentschel, Edward J Goetzl, Mark P Mattson, Dimitrios Kapogiannis

Open access · goldAbstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
4.8field-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

73 citing papers in PubMed, 94 citations in OpenAlex.

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13 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

10 authors at 3 institutions in 1 country.

Carlos J Nogueras-OrtizLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD 21224, USA.ORCID 0000-0003-2503-965X
Vasiliki MahairakiDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Francheska Delgado-PerazaLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD 21224, USA.ORCID 0000-0003-0201-0248
Debamitra DasDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Konstantinos AvgerinosLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD 21224, USA.
Erden ErenLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD 21224, USA.ORCID 0000-0002-5190-9500
Matthew HentschelLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD 21224, USA.ORCID 0000-0002-5210-6144
Edward J GoetzlDepartment of Medicine, University of California, San Francisco, CA 94143, USA.
Mark P MattsonDepartment of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Dimitrios KapogiannisLaboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, MD 21224, USA.ORCID 0000-0003-2181-3118
National Institutes of Health · USJohns Hopkins University · USUniversity of California, San Francisco · US

Funding

Studies in Dementia and Neurodegenerative DiseasesZIAAG000975 · NIA · NATIONAL INSTITUTE ON AGING · PI KAPOGIANNIS, DIMITRIOS · 2009 to 2025
$31.5M
6 · The paper itself

Abstract

We have previously shown that blood astrocytic-origin extracellular vesicles (AEVs) from Alzheimer's disease (AD) patients contain high complement levels. To test the hypothesis that circulating EVs from AD patients can induce complement-mediated neurotoxicity involving Membrane Attack Complex (MAC) formation, we assessed the effects of immunocaptured AEVs (using anti-GLAST antibody), in comparison with neuronal-origin (N)EVs (using anti-L1CAM antibody), and nonspecific CD81+ EVs (using anti-CD81 antibody), from the plasma of AD, frontotemporal lobar degeneration (FTLD), and control participants. AEVs (and, less effectively, NEVs) of AD participants induced Membrane Attack Complex (MAC) expression on recipient neurons (by immunohistochemistry), membrane disruption (by EthD-1 assay), reduced neurite density (by Tuj-1 immunohistochemistry), and decreased cell viability (by MTT assay) in rat cortical neurons and human iPSC-derived neurons. Demonstration of decreased cell viability was replicated in a separate cohort of autopsy-confirmed AD patients. These effects were not produced by CD81+ EVs from AD participants or AEVs/NEVs from FTLD or control participants, and were suppressed by the MAC inhibitor CD59 and other complement inhibitors. Our results support the stated hypothesis and should motivate future studies on the roles of neuronal MAC deposition and AEV/NEV uptake, as effectors of neurodegeneration in AD.

Indexed as

AnimalsAstrocytesCase-Control StudiesCD59 AntigensCells, CulturedComplement ActivationComplement Membrane Attack ComplexEnzyme-Linked Immunosorbent AssayExtracellular VesiclesHumansInduced Pluripotent Stem CellsMaleNeuronsRatsCD59 AntigensCD59 protein, humanComplement Membrane Attack Complexastrocytescomplementexosomesmembrane attack complexneurodegeneration

Identifiers

PMID32635578
PMCPMC7407141
OpenAlexW3038782452

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.