# Mechanisms contributing to co-morbid psychosis in Alzheimer's disease

> **NIH VA I01** · SOUTH TEXAS VETERANS HEALTH CARE SYSTEM · 2022 · —

## Abstract

Project Summary/Abstract:
Psychotic symptoms (hallucinations and delusions) are highly prevalent Alzheimer's disease. Unfortunately, the
antipsychotic medications used to treat psychosis are contraindicated in the elderly where the Food and Drug
Administration (FDA) issued a black-box warning for all first- and second-generation antipsychotic medications
indicating that these drugs increase the risk of death in elderly dementia patients. We have demonstrated that
the hippocampus plays a central role in the regulation of dopamine system function and that aberrant
hippocampal regulation of dopamine neuron activity likely contributes to psychosis in schizophrenia. Given that
the hippocampus is a key site of pathology in AD, we posit that the hippocampus may be a site of convergence
contributing to comorbid psychosis in AD, and we will use rodent models to study this hypothesis. Specifically,
we will examine basal activity and afferent regulation of dopamine neuron activity as well as behavioral correlates
of psychosis in two distinct rodent models of AD (Aim 1). We will then examine the consequence of AD pathology
on vHipp interneuron function and whether transplantation of stem cell derived interneurons (Aim 2) or
pharmacological modulation of hippocampal function (Aim 3) can reverse aberrant neuronal activity and
behavior in AD models. This proposal with therefore identify a potential novel therapeutic target and inform the
development of more effective treatment approaches for AD and comorbid psychosis.

## Key facts

- **NIH application ID:** 10293545
- **Project number:** 5I01BX004646-02
- **Recipient organization:** SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
- **Principal Investigator:** Daniel Lodge
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10293545

## Citation

> US National Institutes of Health, RePORTER application 10293545, Mechanisms contributing to co-morbid psychosis in Alzheimer's disease (5I01BX004646-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10293545. Licensed CC0.

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