Evidence map›Paper›PMID 41947859›Full record

ArticleFrontiers in neuroscience2026

Pre-analytical characterization of CNS-derived extracellular vesicles from human saliva: effect of room temperature and cellular origin.

Luciano M Licatini, Luigi M Licatini, Fadi A Haddadin, Grace C Conklin, AmanPreet Badhwar, Floyd M Sarsoza, Sonal Sukreet, Charisse N Winston

Abstract read
In one paragraph

Article in Frontiers in neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Review
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

8 authors.

Luciano M Licatini *Alzheimer's Therapeutic Research Institute - Neuroscience Translational Research Division, Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, San Diego, CA, United States.
Luigi M Licatini *Alzheimer's Therapeutic Research Institute - Neuroscience Translational Research Division, Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, San Diego, CA, United States.
Fadi A Haddadin *Alzheimer's Therapeutic Research Institute - Neuroscience Translational Research Division, Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, San Diego, CA, United States.
Grace C ConklinAlzheimer's Therapeutic Research Institute - Neuroscience Translational Research Division, Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, San Diego, CA, United States.
AmanPreet BadhwarMultiomics Investigation of Neurodegenerative Diseases (MIND) Lab, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, QC, Canada.
Floyd M SarsozaAlzheimer's Therapeutic Research Institute - Neuroscience Translational Research Division, Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, San Diego, CA, United States.
Sonal SukreetAlzheimer's Therapeutic Research Institute - Neuroscience Translational Research Division, Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, San Diego, CA, United States.
Charisse N WinstonAlzheimer's Therapeutic Research Institute - Neuroscience Translational Research Division, Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, San Diego, CA, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Blood-derived extracellular vesicles (EVs) from neurons and astrocytes carrying Alzheimer's disease (AD) biomarkers can predict progression from mild cognitive impairment (MCI) to AD; however, their potential in saliva remains largely unexplored. Saliva-derived extracellular vesicles (sEVs) represent a promising non-invasive biomarker source for AD and other age-related dementias (ADRD), but progress has been limited by a lack of standardized protocols for saliva collection, storage, and central nervous system (CNS)-derived EV isolation. Methods: This study had two primary objectives: (1) to optimize enrichment of CNS cell-specific sEVs from the same individuals, and (2) to evaluate the impact of cellular origin and storage temperature (room temperature, 4°C, -20°C) on the stability and quantification of AD-related biomarkers and inflammatory cytokines. Saliva was collected via passive drool from participants in the Nathan Shock Healthy Aging Study (mean age 71.3 years; n = 15). EVs of neuronal, astrocytic, microglial, and oligodendrocyte origin were isolated using ExoQuick-TC precipitation followed by magnetic bead immunocapture. Executive function and attention were assessed using the NIH Toolbox Cognition Battery. Biomarkers were quantified using high-sensitivity immunoassays (MSD, SIMOA Qunaterix). Results: Astrocyte-derived EVs demonstrated significant enrichment of key AD biomarkers, including Aβ40, Aβ42, and total tau. Phosphorylated tau (p-tau217) was largely undetectable across all fractions. TDP-43 was most abundant in EV-depleted saliva, while inflammatory cytokines were broadly distributed across all fractions. Storage temperature did not consistently alter biomarker levels; however, -20°C storage yielded optimal biomarker quantification. Importantly, lower levels of inflammatory cytokines (IFN-γ, IL-10, and IL-6) in EV-depleted saliva were associated with better working memory performance. Discussion: This study provides proof-of-concept validation for the characterization and comparison of multiple CNS-derived salivary EV fractions within the same individuals. The findings support saliva as a feasible, non-invasive matrix for assessing neurodegenerative and neuroinflammatory biomarkers. Establishing a standardized methodology for salivary EV isolation and storage lays the groundwork for future longitudinal studies aimed at diagnosing and predicting AD progression using saliva-based biomarkers.

Indexed as

Alzheimer’s diseasebiomarkersextracellular vesiclespre-analytical measuressalivastorage temperature

Identifiers

PMID41947859
PMCPMC13050933

What Socratic 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 Socratic graph.