# 4-Nonylphenol and the Mechanism of Alzheimer's Disease

> **NIH NIH U54** · UNIVERSITY OF TEXAS EL PASO · 2022 · $380,000

## Abstract

Project Summary
 Alzheimer's disease (AD) is a progressive brain disorder associated with continuous decline
in thinking that leads to loss of behavioral, social, and cognitive skills. Memory loss is the key
symptom of AD. It is a major public health concern and a tremendous economic and societal
challenge. Minority communities, such as Hispanic and Black, are disproportionately affected by
this disease. AD is a neurodegenerative disease, and its pathology is characterized by extensive
neuronal loss and the deposition of two abnormal protein structures, amyloid plaques (composed
of amyloid -protein) and neurofibrillary tangles (composed of the microtubule-associated protein,
Tau) in the affected brain regions. Aging is the most consistent risk factor in developing AD and
recent evidence suggests that environmental factors play a significant role in this process.
4-
Nonylphenol (4-NP)
is an endocrine-disrupting compound (EDC) and an environmental pollutant
that has recently been implicated as a risk factor for AD and AD-related dementia. 4-NP
has been
of environmental concern for decades due of its toxicity, estrogenic properties, and widespread
contamination in the environment including water, air, and soil.
Research from our laboratory
demonstrates that 4-NP disrupts microtubules (MT) and alters the localization and expression of
Tau, the MT-associated protein. The Tau protein and its phosphorylation status has been shown
to be linked to the initiation and progression of AD and AD-related dementia. Earlier studies have
exhibited that 4-NP exposure produces learning and memory impairment in adult rats and causes
behavioral and cognitive deficits in offspring when exposed prenatally. Our preliminary studies
indicate that 4-NP causes a substantial neuronal loss in zebrafish embryos. Altogether, these
results point towards the adverse effects of 4-NP on neuronal development, neurodegeneration,
and learning/memory. Therefore, our hypothesis is that exposure of 4-NP can induce AD-like
pathology and behavior by disrupting the cytoskeleton and inducing tau hyperphorylation and
protein aggregation. Both cell cultures and a zebrafish model will be used to conduct the study.
We will test our hypothesis by addressing the following two specific aims. In Aim-1, we will
determine the
mechanism of 4-NP-induced cytoskeletal disruption and Tau
hyperphosphorylation in a cell culture
model. The goal of Aim-2 is to utilize the zebrafish model
to study the effects of 4-NP on learning and memory deficits. It is anticipated that the proposed
study will delineate the mechanism by which 4-NP induces AD and related dementia, which affect
the Hispanic population in U.S./Mexico border communities disproportionately.

## Key facts

- **NIH application ID:** 10499744
- **Project number:** 3U54MD007592-29S6
- **Recipient organization:** UNIVERSITY OF TEXAS EL PASO
- **Principal Investigator:** Robert A. Kirken
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $380,000
- **Award type:** 3
- **Project period:** 1998-06-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499744

## Citation

> US National Institutes of Health, RePORTER application 10499744, 4-Nonylphenol and the Mechanism of Alzheimer's Disease (3U54MD007592-29S6). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499744. Licensed CC0.

---

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