Evidence map›Paper›PMID 36213994›Full record

ArticleJournal of Alzheimer's disease : JAD2022

Brain Tissue-Derived Extracellular Vesicles in Alzheimer's Disease Display Altered Key Protein Levels Including Cell Type-Specific Markers.

Yiyao Huang, Tom A P Driedonks, Lesley Cheng, Harinda Rajapaksha, David A Routenberg, Rajini Nagaraj, Javier Redding, Tanina Arab, Bonita H Powell, Olga Pletniková and 5 more

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

Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 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

15 authors at 4 institutions in 3 countries.

Yiyao HuangDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tom A P DriedonksDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lesley ChengDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
Harinda RajapakshaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
David A RoutenbergMeso Scale Diagnostics, LLC, Rockville, MD, USA.
Rajini NagarajMeso Scale Diagnostics, LLC, Rockville, MD, USA.
Javier ReddingDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tanina ArabDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bonita H PowellDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Olga PletnikováDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Juan C TroncosoDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lei ZhengDepartment of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Andrew F HillDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
Vasiliki MahairakiDepartment of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kenneth W WitwerDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Johns Hopkins University · USLa Trobe University · AUMeso Scale Discovery (United States) · USNanfang Hospital · CN

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3M
Biomarkers of Cognitive Decline among Normal Individuals: The BIOCARD cohortU01AG033655 · NIA · JOHNS HOPKINS UNIVERSITY · PI ALBERT, MARILYN S. · 2009 to 2013
$11.2M
Next-generation extracellular vesicle biologics to target central nervous system and peripheral reservoirs of HIVR01AI144997 · NIAID · JOHNS HOPKINS UNIVERSITY · PI RAMRATNAM, BHARAT, WITWER, KENNETH W · 2019 to 2023
$4.0M
Extracellular Vesicle and Extracellular RNA Biomarkers of HIV-1 Central Nervous System Pathogenesis and Cigarette UseR01DA047807 · NIDA · JOHNS HOPKINS UNIVERSITY · PI WITWER, KENNETH W · 2018 to 2022
$3.7M
Surface Signatures of Neuronal and Glial Extracellular VesiclesUH3MH118167 · NIMH · MESO SCALE DIAGNOSTICS, LLC · PI ROUTENBERG, DAVID AARON · 2020 to 2022
$2.7M
Novel Approaches to Capture, Sorting, and Characterization of CNS-Origin Extracellular VesiclesR33MH118164 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MACHAIRAKI, VASILIKI, WITWER, KENNETH W · 2020 to 2022
$2.2M
Novel Separation Methods for exRNA Carriers: Extracellular Vesicles, Lipoprotein Particles, and Protein AggregatesUH3CA241694 · NCI · JOHNS HOPKINS UNIVERSITY · PI WITWER, KENNETH W · 2021 to 2022
$1.1M
Novel Separation Methods for exRNA Carriers: Extracellular Vesicles, Lipoprotein Particles, and Protein AggregatesUG3CA241694 · NCI · JOHNS HOPKINS UNIVERSITY · PI WITWER, KENNETH W · 2019 to 2020
$941k
Novel Approaches to Capture, Sorting, and Characterization of CNS-Origin Extracellular VesiclesR21MH118164 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MACHAIRAKI, VASILIKI, WITWER, KENNETH W · 2018 to 2019
$471k
Surface Signatures of Neuronal and Glial Extracellular VesiclesUH2MH118167 · NIMH · MESO SCALE DIAGNOSTICS, LLC · PI ROUTENBERG, DAVID AARON · 2018 to 2019
$444k
NCI NIH HHS UG3 CA241694NCI NIH HHS UH3 CA241694NIAID NIH HHS R01 AI144997NIA NIH HHS P30 AG066507NIA NIH HHS U01 AG033655NIDA NIH HHS R01 DA047807NIMH NIH HHS R21 MH118164NIMH NIH HHS R33 MH118164NIMH NIH HHS UH2 MH118167NIMH NIH HHS UH3 MH118167
6 · The paper itself

Abstract

backgroundBrain tissue-derived extracellular vesicles (bdEVs) play neurodegenerative and protective roles, including in Alzheimer's disease (AD). Extracellular vesicles (EVs) may also leave the brain to betray the state of the CNS in the periphery. Only a few studies have profiled the proteome of bdEVs and source brain tissue. Additionally, studies focusing on bdEV cell type-specific surface markers are rare.

objectiveWe aimed to reveal the pathological mechanisms inside the brain by profiling the tissue and bdEV proteomes in AD patients. In addition, to indicate targets for capturing and molecular profiling of bdEVs in the periphery, CNS cell-specific markers were profiled on the intact bdEV surface.

methodsbdEVs were separated and followed by EV counting and sizing. Brain tissue and bdEVs from age-matched AD patients and controls were then proteomically profiled. Total tau (t-tau), phosphorylated tau (p-tau), and antioxidant peroxiredoxins (PRDX) 1 and 6 were measured by immunoassay in an independent bdEV separation. Neuron, microglia, astrocyte, and endothelia markers were detected on intact EVs by multiplexed ELISA.

resultsOverall, concentration of recovered bdEVs was not affected by AD. Proteome differences between AD and control were more pronounced for bdEVs than for brain tissue. Levels of t-tau, p-tau, PRDX1, and PRDX6 were significantly elevated in AD bdEVs compared with controls. Release of certain cell-specific bdEV markers was increased in AD.

conclusionSeveral bdEV proteins are involved in AD mechanisms and may be used for disease monitoring. The identified CNS cell markers may be useful tools for peripheral bdEV capture.

Indexed as

Alzheimer DiseaseExtracellular VesiclesBrainHumansNeuronsProteomeProteomeAlzheimer’s diseasebraincell of origin markerscentral nervous systemectosomesexosomesextracellular vesiclesmicrovesiclesproteomics

Identifiers

PMID36213994
PMCPMC9741741
OpenAlexW4300981921

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.