# Accelerating Treatment Development for Psychosis in AD: MODEL-AD+P - Supplement

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $158,127

## Abstract

Administrative Supplement to Accelerating Treatment Development for Psychosis in AD: MODEL AD+P
 Psychotic symptoms occur in ~ 40-60% of individuals with Alzheimer Disease (AD with psychosis, AD+P).
Numerous studies have found that the AD+P phenotype is associated with more rapid cognitive decline than AD
subjects without psychosis (AD-P). Current, empirically developed treatments for psychosis in AD have limited
efficacy, do not alter the more rapid disease progression, and are associated with substantial toxicity, including
excess mortality. MODEL AD+P was funded with the goal of closing several critical gaps in knowledge that
currently inhibit effective treatment development for psychosis in AD. We were funded to accomplish this goal
by conducting a set of integrated experiments that include: Aim 1) more finely resolve signaling alterations in
AD+P by characterizing the post-synaptic density (PSD) phosphoproteome and kinome signature of AD+P, and;
Aim 2) test computationally identified drugs, including the CCR5 inhibitor, maraviroc, for effects on the PSD
protein and phosphoprotein signature in 3 mouse models of AD pathology (5XFAD, APPSAA, hTau) in
comparison to WT mice.
 We now request an administrative supplement designed to increase the likely impact of the funded research
objectives of MODEL AD+P on treatment development for AD+P. We propose to accomplish this in two
Supplemental Aims. Supplemental Aim 1 enhances our understanding of maraviroc's effects on the PSD
proteome in the 5xFAD, APPSAA and hTau mouse models by testing the impact of maraviroc treatment on post
synaptic structural dynamics of dendritic spines and on behavioral tests of learning/memory in these same
mouse models. In Supplemental Aim 2, we will then integrate maraviroc's effects on spine dynamics and
learning with findings from the currently funded Aims in which we will have: characterized the PSD proteome
and phosphoproteome after maraviroc treatment in these models and more deeply characterized the PSD
proteome, phosphoproteome, and kinome signature of AD+P.
 These Supplemental Aims do not represent a change in the scope of MODEL AD+P. The primary research
objective remains consistent, focusing on the PSD proteome in AD+P. The Supplement Aims enriching our
existing framework without altering the fundamental direction of the research. If successful, these Supplemental
Aims will augment MODEL AD+P's primary purpose: to accelerate development of experimental therapeutics
for AD+P. Specifically, these Supplemental Aims will link the understanding of the PSD proteome of AD+P
generated by the currently funded study directly to post-synaptic structural changes of a fundamental plasticity
mechanism, dendritic spine structural dynamics. In so doing we will be positioned to identify additional targets
(and drugs for these targets) that can be tested for therapeutic impact, and via our data and resource sharing
plan, similarly enable investigation of potential new treatments b...

## Key facts

- **NIH application ID:** 11041361
- **Project number:** 3R01MH116046-07S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Julia K Kofler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $158,127
- **Award type:** 3
- **Project period:** 2018-09-25 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11041361

## Citation

> US National Institutes of Health, RePORTER application 11041361, Accelerating Treatment Development for Psychosis in AD: MODEL-AD+P - Supplement (3R01MH116046-07S1). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/11041361. Licensed CC0.

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