Evidence map›Paper›PMID 34925024›Full record

ArticleFrontiers in pharmacology2021

Multi-Omics Analysis of Microglial Extracellular Vesicles From Human Alzheimer's Disease Brain Tissue Reveals Disease-Associated Signatures.

Whitaker Cohn, Mikhail Melnik, Calvin Huang, Bruce Teter, Sujyoti Chandra, Chunni Zhu, Laura Beth McIntire, Varghese John, Karen H Gylys, Tina Bilousova

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

Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 2 pooled it
7.0field-weighted citation impact, top 2% 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

85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.

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  10. Increased circulating TREM2Brain, behavior, & immunity - health · 2026
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25 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 2 institutions in 1 country.

Whitaker CohnDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.
Mikhail MelnikSchool of Nursing, University of California, Los Angeles, Los Angeles, CA, United States.
Calvin HuangSchool of Nursing, University of California, Los Angeles, Los Angeles, CA, United States.
Bruce TeterDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.
Sujyoti ChandraDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.
Chunni ZhuDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.
Laura Beth McIntireTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, United States.
Varghese JohnDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.
Karen H GylysSchool of Nursing, University of California, Los Angeles, Los Angeles, CA, United States.
Tina BilousovaDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.
University of California, Los Angeles · USColumbia University Irving Medical Center · US

Funding

Tau pathology in neurons, glia, and cell type-specific exosomes from cryopreserved AD cortexR21AG063767 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BILOUSOVA, TINA, GYLYS, KAREN H · 2020 to 2020
$429k
NIA NIH HHS R21 AG063767
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the most common cause of dementia, yet there is no cure or diagnostics available prior to the onset of clinical symptoms. Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are released from almost all types of cell. Genome-wide association studies have linked multiple AD genetic risk factors to microglia-specific pathways. It is plausible that microglia-derived EVs may play a role in the progression of AD by contributing to the dissemination of insoluble pathogenic proteins, such as tau and Aβ. Despite the potential utility of EVs as a diagnostic tool, our knowledge of human brain EV subpopulations is limited. Here we present a method for isolating microglial CD11b-positive small EVs from cryopreserved human brain tissue, as well as an integrated multiomics analysis of microglial EVs enriched from the parietal cortex of four late-stage AD (Braak V-VI) and three age-matched normal/low pathology (NL) cases. This integrated analysis revealed 1,000 proteins, 594 lipids, and 105 miRNAs using shotgun proteomics, targeted lipidomics, and NanoString nCounter technology, respectively. The results showed a significant reduction in the abundance of homeostatic microglia markers P2RY12 and TMEM119, and increased levels of disease-associated microglia markers FTH1 and TREM2, in CD11b-positive EVs from AD brain compared to NL cases. Tau abundance was significantly higher in AD brain-derived microglial EVs. These changes were accompanied by the upregulation of synaptic and neuron-specific proteins in the AD group. Levels of free cholesterol were elevated in microglial EVs from the AD brain. Lipidomic analysis also revealed a proinflammatory lipid profile, endolysosomal dysfunction, and a significant AD-associated decrease in levels of docosahexaenoic acid (DHA)-containing polyunsaturated lipids, suggesting a potential defect in acyl-chain remodeling. Additionally, four miRNAs associated with immune and cellular senescence signaling pathways were significantly upregulated in the AD group. Our data suggest that loss of the homeostatic microglia signature in late AD stages may be accompanied by endolysosomal impairment and the release of undigested neuronal and myelin debris, including tau, through extracellular vesicles. We suggest that the analysis of microglia-derived EVs has merit for identifying novel EV-associated biomarkers and providing a framework for future larger-scale multiomics studies on patient-derived cell-type-specific EVs.

Indexed as

Alzheimer’s diseaseexosomesextracellular vesiclesmicrogliaomics analysis

Identifiers

PMID34925024
PMCPMC8675946
OpenAlexW4200525770

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.