# Development of Blood-based Circular RNA Biomarkers for Alzheimer's Disease

> **NIH NIH R43** · VIVID GENOMICS, INC. · 2022 · $508,467

## Abstract

PROJECT SUMMARY—This Phase I application targets PAS-19-316 to address the priorities for a) new, cost-
effective, minimally-invasive biomarkers that could be used for screening and b) research that would identify new
biomarkers that could serve as surrogate measures for disease progression in Alzheimer’s Disease and Related
Dementias (AD/ADRD). Specifically, Vivid Genomics is exploring the use of circular RNAs (circRNAs) in blood
as a biomarker of AD and AD progression, including the possible identification of presymptomatic AD. The
enormous public health challenge of AD is complicated by the lack of accessible, non-invasive tools for
definitively diagnosing the disease prior to death. Although imaging and AD biomarkers in cerebrospinal fluid
(CSF) can provide insight into disease status, they are not ideal for routine screening. Recently reported blood-
based screens for amyloid b and phosphorylated tau (p-tau) represent a significant advance, but they require
methods that are not easily scalable or may not have adequate sensitivity in early disease. In addition, they
assess the presence of amyloid b and p-tau at a particular point in time and cannot currently be used to indicate
the rate of disease progression or future likelihood of decline. Thus, developing new scalable, cost-effective,
minimally-invasive blood-based biomarkers could provide a much-needed tool for routine screening in high-risk
individuals, routine follow-up to track AD progression, or ongoing monitoring to assess treatment efficacy. Recent
findings indicate several circRNAs differentially expressed in the brains of patients with and without AD are
significantly associated with AD diagnosis, clinical severity, and neuropathological severity. In addition, changes
in circRNA expression can be detected even in presymptomatic patients. Preliminary studies indicate these
markers are also differentially expressed in blood, providing a basis for exploring blood-based circRNAs as
biomarkers of AD and/or AD progression. In this proof-of-concept Phase I SBIR, Vivid proposes to identify
multiple circRNAs whose expression in blood is associated with AD diagnosis, clinical severity, and/or neuro-
pathological severity. Aim. Identify blood-based circRNAs that are associated with AD status and AD-
biomarker positivity. RNA-seq will be used to analyze circRNAs in blood from 300 patients in the Knight
Alzheimer's Disease Research Center cohort. A rank-ordered list of circRNAs of interest will be developed based
on the strength of their association with AD traits adjusted for median transcript integrity score, age of onset,
batch, sex, and genetic ancestry. Associations and rank order will then be validated in blood from 300 patients
in the AD Neuroimaging Initiative (ADNI) cohort. Go/No-Go Criterion: Identify ≥ 2 blood-based circRNAs
correlated with one or more AD traits (FDR < 0.05). Impact—Proof-of-concept would provide a foundation for
development of blood-based circRNAs as biomarkers of ...

## Key facts

- **NIH application ID:** 10480165
- **Project number:** 1R43AG076106-01A1
- **Recipient organization:** VIVID GENOMICS, INC.
- **Principal Investigator:** Julie Collens
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $508,467
- **Award type:** 1
- **Project period:** 2022-06-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480165

## Citation

> US National Institutes of Health, RePORTER application 10480165, Development of Blood-based Circular RNA Biomarkers for Alzheimer's Disease (1R43AG076106-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10480165. Licensed CC0.

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