# Aplysia as a test of the viral theory of aging

> **NIH NIH P40** · UNIVERSITY OF MIAMI ROSENTEIL SCHOOL · 2021 · $258,875

## Abstract

Alzheimer’s Disease (AD) is a complex, chronic syndrome, likely with multiple underlying etiologies. In spite of
considerable investment, most therapeutic strategies tested to date have had disappointing outcomes. This
suggests the need to explore additional model systems that will allow different approaches to testing current as
well as alternative hypotheses about the etiology of AD and its related dementias (ADRD). The sea hare
Aplysia californica (Aplysia) is a widely used model of neuronal cell function and the cellular basis of learning
and memory. Aplysia exhibits a predictable aging process leading to senescence and death at age 12 months.
Our research has shown that Aplysia is an excellent model of aging wherein behavioral, neurophysiological,
and transcriptomic analyses can be combined to understand fundamental processes in nervous system aging.
Aplysia and other mollusks have been demonstrated to be evolutionarily closer to mammals than ecdysozoan
models of AD (Drosophila and C. elegans). We recently demonstrated that Aplysia expresses a variety of
genes orthologous to those implicated in AD progression, underscoring the relevance of this model. Moreover,
a natural viral infection has been identified in the nervous system of Aplysia, which may be similar to viral
infections of the human brain that recently have been suggested to contribute to the onset of the amyloid
proteinopathies that define AD. Recent data from our laboratory also show that viral load increases with age
and may affect the aging process. Here we propose a 1-year study to test the aging Aplysia model as a model
of virus-induced AD and ADRD, primarily by employing new models to analyze the Aplysia nervous system
transcriptome in the context of a naturally occurring viral infection that increases with age. We will also
leverage the large neurons of Aplysia to perform single cell transcriptomics in a single cell model of the effects
of human mutant tau protein. This approach is based on many unique advantages of the Aplysia system for
these studies. We will explore development of this model through three proposed aims: (1) Transfection of
buccal S cluster sensory neurons (BSC) with mutant tau mRNA combined with single cell RNA sequencing will
elucidate whether these transfections mimic the transcriptional phenotype of AD. (2) We will use an age-viral
load covariate statistical model to compare low vs. high viral load Aplysia sensory neuron RNA sequencing
data from our current datasets to determine the effects of viral load on the aging transcriptome and as a model
for virus-induced sporadic AD. (3) We will identify potential novel antimicrobial peptides (AMP) in yet to be
annotated Aplysia transcripts using motif identification-based methods to identify AMP with the capacity to form
protein aggregates in a manner similar to that of amyloid beta (Aβ) and thus serve as more informed
candidates for models of Aβ’s AMP-like activity. The proposed research provides a targeted...

## Key facts

- **NIH application ID:** 10289803
- **Project number:** 3P40OD010952-26S1
- **Recipient organization:** UNIVERSITY OF MIAMI ROSENTEIL SCHOOL
- **Principal Investigator:** LYNNE A FIEBER
- **Activity code:** P40 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $258,875
- **Award type:** 3
- **Project period:** 1996-05-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289803

## Citation

> US National Institutes of Health, RePORTER application 10289803, Aplysia as a test of the viral theory of aging (3P40OD010952-26S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10289803. Licensed CC0.

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