# Altered reverse transcriptase-dependent gene diversification mechanisms in Alzheimer's disease

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2022 · $16,760

## Abstract

PROJECT SUMMARY/ABSTRACT
Somatic gene recombination (SGR) may increase gene copy number and diversity of disease-relevant genes
that contribute to age-related neurodegeneration. The proposed SGR mechanism requires gene transcription,
reverse transcription of RNA by an endogenous reverse transcriptase (RT), and DNA strand breaks at sites that
enable retro-insertion. However, detailed studies on endogenous reverse transcriptase activity in the normal
and diseased human brain is virtually unknown. Furthermore, the identity and possible diversity of endogenous
reverse transcriptase genes in the human brain has yet to be defined. A strong candidate is the long interspersed
nuclear element, LINE1 (L1), that was long thought to be a dead evolutionary remnant of ancient RNA viruses.
There are hundreds of thousands of LINE1 sequences in our human genomes and some are clearly active.
Based upon sequence data, each LINE1 element contains a potentially active or activatable endogenous reverse
transcriptase gene that encodes a likely RT protein, ORF2p, with reverse transcriptase and endonuclease
activities. LINE1 is a known mediator of global chromosomal instability, genomic instability, and genetic
heterogeneity and has been implicated in the progression of cancer, aging, and multiple neurodegenerative
diseases. Candidate Juliet Nicodemus’ project and training program will fall within the parental R01’s Aim 3, and
we added additional granularity for this supplement as part of her focused pursuit of Aim 3, as well as to enable
optimal training experiences. She will pursue the central hypothesis that diverse forms of functional reverse
transcriptases differ in the normal and AD human brain.

## Key facts

- **NIH application ID:** 10509210
- **Project number:** 3R01AG065541-02S1
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** JEROLD CHUN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $16,760
- **Award type:** 3
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10509210

## Citation

> US National Institutes of Health, RePORTER application 10509210, Altered reverse transcriptase-dependent gene diversification mechanisms in Alzheimer's disease (3R01AG065541-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10509210. Licensed CC0.

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