# Developing Aplysia as a Model of Alzheimer's Disease

> **NIH NIH P40** · UNIVERSITY OF MIAMI ROSENTEIL SCHOOL · 2020 · $114,454

## 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. Here
we propose an 8 month study to rapidly assess the potential usefulness of Aplysia as a model
for AD and ADRD and specifically to evaluate the role of viral infection in these pathologies.
This approach is based on many unique advantages of the Aplysia system for these studies.
Aplysia exhibits a predictable aging process leading to senescence and death at age 12
months. We have recently 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). Aplysia expresses a variety of genes orthologous to those
implicated in AD progression. Furthermore, Aplysia has been successfully used as an induced
model of tauopathies known to occur in AD. This suggests Aplysia has potential as a model for
AD research. Recently, viral infections of the human brain have been suggested to contribute to
the onset of the amyloid proteinopathies that define AD. Similarly, a natural viral infection has
been identified in the nervous system of Aplysia. Recent data from our laboratory suggest that
viral load increases with age, and may affect the aging process. We currently have two
transcriptional datasets derived from Aplysia sensory neurons that span maturity through
advanced age and varying viral load. Accompanying these datasets are behavioral and
morphological phenotypes of each individual. We propose to use these datasets to determine if
Aplysia neurons exhibit ADRD-like transcriptional changes in age and if those changes may be
driven by viral infection. The proposed research provides a targeted and unique opportunity to
evaluate the potential usefulness of Aplysia as a model of AD and ADRD and test hypotheses
on the role of infections and accompanying immune responses on development of these
disease processes.

## Key facts

- **NIH application ID:** 10123703
- **Project number:** 3P40OD010952-25S1
- **Recipient organization:** UNIVERSITY OF MIAMI ROSENTEIL SCHOOL
- **Principal Investigator:** LYNNE A FIEBER
- **Activity code:** P40 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $114,454
- **Award type:** 3
- **Project period:** 1996-05-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123703

## Citation

> US National Institutes of Health, RePORTER application 10123703, Developing Aplysia as a Model of Alzheimer's Disease (3P40OD010952-25S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10123703. Licensed CC0.

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