# Human Endogenous retroviruses as potential early markers for Alzheimer's disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $346,716

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) is a neurodegenerative disorder that is marked by progressive damage and loss of
neurons in the central nervous system. Current diagnosis of Alzheimer's disease relies largely on documenting
mental decline, at which point Alzheimer's has already caused severe brain damage. There is an urgent need
for novel methods to detect Alzheimer's before these devastating symptoms begin. Identifying pending cognitive
impairment at an early stage can help design interventions that may reduce the risk of cognitive decline. Human
Endogenous Retroviruses (ERVs) have integrated into mammalian genome over millions of years and comprise
up to 5–8% of the human genome, as compared to 1-2% of protein coding sequences. Compared to the
numerous studies describing proteins and their functions, very few studies have been performed on the impact
of human ERVs on health and disease. Understanding how each ERV modulates both itself and its related
genomic elements – functional proteins, disease-associated antigens, or genomic regulators – is crucial in
determining the impact that ERVs can have on human health and diseases. ERVs have been reported to be
transcriptionally active in the brains of AD patients. In addition, ERV activation is also associated with cognitive
impairment in mice. In the parent grant, NIH/NCI R01CA226570 “Aggressive prostate cancer of African
Americans is correlated with regulation of immunoregulatory genes in stroma”, we proposed that an epigenetic
control of the antiviral immune response pathways via ERVs in prostate tumor microenvironment may contribute
to differences in prostate cancer progression among patients of different racial groups. ERVs are highly repetitive
and present in multiple copies throughout genome making it difficult to study them using existing computational
tools. Most studies use PCR that can detect a few ERVs. We have developed a computational tool to study
ERVs at the genome level, allowing detection of ERV changes at the global level. Applying this novel
computational method, we have been able to correlate clinical outcomes with ERVs expression in prostate and
cervical cancer. Here, we propose to extend these studies to AD and hypothesize that changes in ERV activation
contribute to the inflammation and pathophysiology in AD. We will examine our hypothesis in two aims. First, we
will investigate the global changes in ERV expression in peripheral blood mononuclear cells (PBMCs) from AD
and mild cognitive impairment (MCI) patients, as well as healthy individuals (age matched). Second, we will
determine the global changes in ERV expression in hippocampus tissue from all three cohorts (age matched).
Identification of ERV changes may not only provide novel molecular target for strategies aimed at attenuating
retroviral element sensing to treat dementia and neuropsychiatric disorders, but may also serve as potential early
biomarkers for AD.

## Key facts

- **NIH application ID:** 10493715
- **Project number:** 3R01CA226570-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Farah Bakhshian Rahmatpanah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $346,716
- **Award type:** 3
- **Project period:** 2019-04-03 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10493715

## Citation

> US National Institutes of Health, RePORTER application 10493715, Human Endogenous retroviruses as potential early markers for Alzheimer's disease (3R01CA226570-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10493715. Licensed CC0.

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