# Novel treatments for neuropsychiatric symptoms in Alzheimers Disease (AD): targeting inflammatory injury using three translational anti-inflammatory strategies in a new AD model.

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Alzheimer’s disease (AD) affects 1 in 8 Americans, and is the sixth leading cause of death in the United States.
Nearly a quarter of a million of those living with AD are Veterans, and recent studies have shown that Veterans
have a 60% increased risk of developing AD. Behavioral changes, such as agitation and aggression, confusion,
and dramatic personality changes, termed neuropsychiatric symptoms (NPS) are highly prevalent in AD patients,
and are extremely challenging for caregivers, placing significant emotional and financial burdens on those caring
for patients with AD, yet current pharmacological treatments for NPS, such as antipsychotics, sedative/hypnotics,
anxiolytics, and antidepressants, often have significant adverse effects that outweigh the benefits of these
treatments. Thus, it is critical to develop better therapeutic approaches to NPS in AD patients. In the general
psychiatric literature, there is an emerging idea that inflammation may be a critical contributor to the etiology of
psychiatric conditions including mood disorder, major depression, post-traumatic stress disorder (PTSD), and
even schizophrenia. How inflammatory processes contribute to neuropsychiatric symptoms in AD has not yet
been studied. Neuropsychiatric manifestations in AD patients occur in the context of a progressive
neurodegenerative disease – the characteristic of AD - which produces substantial inflammation, itself, so we
believe it is critical to understand the role of inflammation in NPS specifically in the context of AD, the ultimate
goal of this application.
 This application is based on the emerging idea that brain inflammation may contribute to psychiatric
conditions including depression, post-traumatic stress disorder (PTSD), and even schizophrenia. We propose
the hypothesis that treating neuroinflammation in AD patients will prevent or decrease neuropsychiatric
symptoms such as agitation, aggression, and apathy, with the potential of finding alternative and better
treatments for Veterans with these difficult-to-treat and often devastating behavioral symptoms of AD.
The premise for this grant is based on the literature, our published data, and new preliminary data, which show
that anti-inflammatory treatment treatments directed at interleukin-6 (IL-6) signaling, specifically, will be effective
in attenuating NPS in relevant models. Aim 1 will ask whether evidence of inflammation predicts increased risk
of NPS in a new mouse model of AD (the hAPP knockin mice recently developed at the Riken Institute) - mice
known to exhibit progressive brain inflammation - and will characterize how aged AD mice perform on behavioral
tasks relevant to human NPS. Markers of inflammation to be correlated with behavior will include serum C-
reactive protein and IL-6, which have been strongly associated with many psychiatric disease states. In addition,
neuroinflammation will be assessed by quantifying the number of activated astrocytes (GFAP) and microglia
(Iba1) using con...

## Key facts

- **NIH application ID:** 9665155
- **Project number:** 1I01BX004321-01A1
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Laura L Dugan
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2019-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9665155

## Citation

> US National Institutes of Health, RePORTER application 9665155, Novel treatments for neuropsychiatric symptoms in Alzheimers Disease (AD): targeting inflammatory injury using three translational anti-inflammatory strategies in a new AD model. (1I01BX004321-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9665155. Licensed CC0.

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