# ncRNAs in plasma EVs of AD patients and their discriminatory power as biomarkers

> **NIH NIH RF1** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $2,297,526

## Abstract

Alzheimer's disease is the most common and economically impactful form of dementia.
Approaches based on cerebrospinal fluid and blood have been established to measure the levels
of amyloid beta and hyperphosphorylated tau to facilitate early diagnosis of AD or to monitor the
effects of therapeutics and progression of the disease. Plasma extracellular vesicles (EVs) and
their cargo present an opportunity to isolate and profile molecules associated with human
pathological conditions. We have recently discovered small nucleolar non-coding RNAs
(snoRNAs) highly enriched in plasma EVs of AD patients compared to non-demented controls.
We posit that tau aggregates irreversibly bind snoRNAs preventing them from performing their
normal function resulting in a compensatory increase of their expression in AD brains. Our
hypothesis is that the expression of certain SNORDs and their secretion in neuron derived EVs is
increased with the progression of AD. Small non-coding nucleolar snoRNAs might represent ideal
biomarkers, compared with proteins and/or mRNAs, because of the protective effect of plasma
EV and the unprecedented sensitivity of detection by ddPCR technology – down to single
transcripts.
This proposal's primary goals are: 1) to test and validate the diagnostic accuracy of SNORD115
and SNORD116 ddPCR assays in human plasma; 2) to understand the nature of the associations
between the abundance of particular SNORDs in AD plasma EVs, their expression level in brain,
the disease state and progression, and if there is an association with APOE genotype; 3) to test
for epigenetic mechanisms underlying the changes in abundance of SNORDs, and 4) using AD
mouse models to reveal the effect of amyloid and tau aggregation on ISF, CSF and plasma EVs
cargo. A better understanding of the underlying regulatory genomic, epigenomic, and cellular
mechanisms responsible for the differences in the enrichment of SNORDs in plasma EVs of AD
patients compared to Controls would help understand essential aspects of APOE mediated risk
of AD and in establishing reliable diagnostic strategies.

## Key facts

- **NIH application ID:** 10532000
- **Project number:** 1RF1AG075992-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** RADOSVETA KOLDAMOVA
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,297,526
- **Award type:** 1
- **Project period:** 2022-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10532000

## Citation

> US National Institutes of Health, RePORTER application 10532000, ncRNAs in plasma EVs of AD patients and their discriminatory power as biomarkers (1RF1AG075992-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10532000. Licensed CC0.

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