# Long Non-coding RNAs as Therapeutic Targets and Biomarkers of Alzheimer's Disease and Related Dementias

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $820,553

## Abstract

ABSTRACT
The effective causative therapies for Alzheimer’s Disease (AD) and related dementias (ADRDs) remain elusive
because the patients are often diagnosed at an advanced state of molecular pathology. Clinically difficult differential
diagnosis of early AD is Frontotemporal Dementia (FTD), a progressive neurodegenerative syndrome associated
with Frontotemporal Lobar Degeneration disorders (FTLDs). The development of diagnostic tools and therapies
for AD and ADRDs has been focused on the part of the human genome that encodes proteins. Most of the genome
(97%), however, consists of non-coding RNAs (ncRNAs) which are increasingly recognized as pivotal regulators
of cellular processes. ncRNAs have recently emerged as key regulators of brain functions derailed in AD and
ADRDs. ncRNA longer than 200 nucleotides are generally referred to as long-noncoding RNAs (lncRNAs). We
hypothesize that lncRNAs expressed in specific cortical cells, become de-regulated in AD and FTLDs, and are
eventually released in circulation, making them potentially specific pathology-associated biomarkers and drug
targets. However, systematic approaches to study lncRNA expression patterns in the brain and in liquid biopsies
in the context of AD and FTLDs are few and there is an urgent need to fill this gap in knowledge. The data we
present demonstrate our ability to discover lncRNAs expressed or enriched in specific neural cell-types and
deregulated in the vulnerable cell populations in brains of AD and FTLDs patients. We developed functional
analysis tools to dissect the role of disease biomarker candidate lncRNAs in relevant model systems. We also
obtained material for testing the expression level and the specificity of our lncRNAs biomarker candidates in the
unprecedented combination of samples from Alzheimer’s Disease Neuroimaging Initiative (ADNI), Framingham
Heart Study (FHS), and clinical studies at German Center for Neurodegenerative Diseases (DZNE). In Aim 1 we
will test the hypothesis that the differential expression of lncRNAs in postmortem dorsolateral prefrontal cortex and
hippocampus will discriminate between AD, FTLDs, and control subjects. We have developed a single nucleus
RNA sequencing (snRNAseq) protocol to study the full spectrum of lncRNAs and used this technique to measure
lncRNAs in all major cortical cell-types. Our preliminary data indicate that our newly discovered, cortical cell-type
specific, lncRNAs are deregulated in AD and FTLDs. In Aim 2 we will define the functions of candidate lncRNA
biomarkers in vitro and in vivo to determine the roles of disease-biomarker candidate lncRNAs in relevant model
systems. In Aim 3 we will test the hypothesis that distinct expression patterns of lncRNAs biomarker candidates in
plasma samples of ADNI, FHS, and DZNE studies participants differentiate among cognitively normal elderly
adults, individuals with MCI, and dementia patients meeting clinical criteria for AD or FTLDs. Together, the proposed
experiments will ...

## Key facts

- **NIH application ID:** 10776184
- **Project number:** 1R01AG084624-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** JAN Krzysztof BLUSZTAJN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $820,553
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10776184

## Citation

> US National Institutes of Health, RePORTER application 10776184, Long Non-coding RNAs as Therapeutic Targets and Biomarkers of Alzheimer's Disease and Related Dementias (1R01AG084624-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10776184. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*