# MicroRNAs in CNS-derived extracellular microvesicles as peripheral blood biomarkers for Alzheimer disease

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $675,269

## Abstract

Summary
In this study we propose to address several major challenges in current Alzheimer disease (AD)
biomarker research, specifically: 1) limited accessibility and high expense associated with
neuroimaging measurements, 2) difficulties in developing antibody-based, quantitative protein
assays for most novel candidates and significant variability among existing immunoassays, 3)
invasive sampling inhibiting widespread use of CSF-based biomarkers, 4) low sensitivity/specificity
and/or lack of validation in relatively large cohorts for blood-based markers, and, 5) detection of
AD at early or even preclinical stages. To these ends we will target microRNAs packaged in central
nervous system (CNS) derived extracellular microvesicles (EMVs) in blood plasma. microRNAs are
a class of small, non-coding RNAs playing important roles in many cellular processes by post-
transcriptional regulation of protein levels, and aberrant microRNA expression has become an
emerging theme for a wide variety of diseases including AD and other neurodegenerative
disorders. microRNAs found in body fluids can be routinely and reliably measured by well-
established methods (e.g., RT-PCR), and data shows EMVs transport biomolecules between the
CNS and peripheral blood and their cargo proteins and nucleic acids vary by cell of origin.
Measurement of cargo proteins in such EMVs has shown particular promise in identifying blood-
based biomarkers for AD and mild cognitive impairment (MCI, or prodromal AD). In a pilot R21
study, we employed global profiling of microRNAs in CNS-derived, relatively neuron-specific
(L1CAM-positive) EMVs in plasma and identified many microRNA and other small RNA transcripts
to be differentially expressed between AD and healthy controls, between AD and Parkinson
disease, or between disease stages.
Here, we aim to confirm and validate the identified candidates for AD/MCI diagnosis, differential
diagnosis, and disease progression in several large, well-established cohorts, including
Alzheimer's Disease Research Centers (ADRCs) affiliated with the University of Washington and
University of Pennsylvania, and ADNI (Alzheimer's Disease Neuroimaging Initiative), with cross-
sectional and longitudinal samples collected, along with extensive clinical characterization. In
parallel, we will use global profiling methods to identify additional microRNA candidates in different
CNS cell type- or neuronal subpopulation- specific EMVs in plasma. Finally, to improve early or
pre-clinical diagnosis, we will evaluate potential microRNA biomarkers in a very early MCI cohort,
subjects at elevated risk for AD. Our project design is geared towards the production of a panel of
biomarkers that is more robust, repeatable, and clinically accessible than currently available.

## Key facts

- **NIH application ID:** 10463539
- **Project number:** 5R01AG061383-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Min Shi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $675,269
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463539

## Citation

> US National Institutes of Health, RePORTER application 10463539, MicroRNAs in CNS-derived extracellular microvesicles as peripheral blood biomarkers for Alzheimer disease (5R01AG061383-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10463539. Licensed CC0.

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