Evidence map›Paper›PMID 38958575›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Nanoscale flow cytometry-based quantification of blood-based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease.

Thamara Dayarathna, Austyn D Roseborough, Janice Gomes, Reza Khazaee, Carolina R A Silveira, Kathy Borron, Soojung Yu, Kristy Coleman, Sarah Jesso, Elizabeth Finger and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Increased circulating TREM2Brain, behavior, & immunity - health · 2026
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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

18 authors.

Thamara DayarathnaInstitute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Austyn D RoseboroughVulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.ORCID 0000-0001-7823-8199
Janice GomesRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Reza KhazaeeDepartment of Biology, Western University, London, Ontario, Canada.
Carolina R A SilveiraCognitive Neurology and Alzheimer's Disease Research Centre, Parkwood Institute, St. Joseph's Health Care Centre, London, Ontario, Canada.
Kathy BorronCognitive Neurology and Alzheimer's Disease Research Centre, Parkwood Institute, St. Joseph's Health Care Centre, London, Ontario, Canada.
Soojung YuCognitive Neurology and Alzheimer's Disease Research Centre, Parkwood Institute, St. Joseph's Health Care Centre, London, Ontario, Canada.
Kristy ColemanCognitive Neurology and Alzheimer's Disease Research Centre, Parkwood Institute, St. Joseph's Health Care Centre, London, Ontario, Canada.
Sarah JessoCognitive Neurology and Alzheimer's Disease Research Centre, Parkwood Institute, St. Joseph's Health Care Centre, London, Ontario, Canada.
Elizabeth FingerRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Penny MacDonaldDepartment of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Michael BorrieDepartment of Geriatric Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Jennie WellsDepartment of Geriatric Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Robert BarthaRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Guangyong ZouRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Shawn N WhiteheadVulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Hon S LeongSunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
Stephen H PasternakRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.ORCID 0000-0002-0204-0255

Funding

Canadian Institute for HealthNew Frontiers in Research Fund NFRFT-2022-03327Weston Brain Institute TR170103
6 · The paper itself

Abstract

introductionAccurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure.

methodsWe developed a nanoscale flow cytometry (nFC)-based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls.

resultsCirculating amyloid beta (Aβ), tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, p-tauS235, ubiquitin, and lysosomal-associated membrane protein 1-positive EVs distinguished AD samples. p-tau181, p-tau217, p-tauS235, and ubiquitin-positive EVs distinguished MCI samples. The most sensitive marker for AD distinction was p-tau231, with an area under the receiver operating characteristic curve (AUC) of 0.96 (sensitivity 0.95/specificity 1.0) improving to an AUC of 0.989 when combined with p-tauS235. DISCUSSION: This nFC-based assay accurately distinguishes MCI and AD plasma without EV isolation, offering a rapid approach requiring minute sample volumes. Incorporating nFC-based measurements in larger populations and comparison to "gold standard" biomarkers is an exciting next step for developing AD diagnostic tools. HIGHLIGHTS: Extracellular vesicles represent promising biomarkers of Alzheimer's disease (AD) that can be measured in the peripheral circulation. This study demonstrates the utility of nanoscale flow cytometry for the measurement of circulating extracellular vesicles (EVs) in AD blood samples. Multiple markers including amyloid beta, tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, and p-tauS235 accurately distinguished AD samples from healthy controls. Future studies should expand blood and cerebrospinal fluid-based EV biomarker development using nanoflow cytometry approaches.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognitive DysfunctionExtracellular VesiclesFlow Cytometrytau ProteinsAgedAged, 80 and overFemaleHumansMaleMiddle AgedAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer's diseasebiomarkerdementiaextracellular vesiclemild cognitive impairmentnanoflow cytometry

Identifiers

PMID38958575
PMCPMC11497682

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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.