# 3D Brain Tissue System for Modeling Resilience to Alzheimer's Disease and Drug Discovery

> **NIH NIH R21** · JACKSON LABORATORY · 2022 · $259,650

## Abstract

PROJECT SUMMARY/ABSTRACT
An alternative approach to discovering the causes of Alzheimer’s disease (AD) for the purposes of prevention,
diagnosis, and treatment is to research individuals who remain cognitively healthy despite significant genetic
risk or pathological burden, a phenomenon termed cognitive resilience. Our quest to understand the nature of
cognitive resilience to normal aging and AD in the first genetically diverse AD mouse population (the AD-BXDs)
that models the genetic, transcriptomic, and phenotypic heterogeneity of human late-onset AD yielded novel
targets for resilience-based therapeutics. To rapidly identify compounds that will likely promote cognitive
resilience in preclinical studies (in vivo) and beyond, there is a critical need for a system that recapitulates the
key features of the AD brain including morphology, cell-cell interactions, and neural network functions in a dish
(in vitro). We propose to develop a 3D co-culture system with neurons, astrocytes, and microglia that exploits
established differences in the onset and progression of cognitive symptoms in the AD-BXDs to investigate
cellular resilience to AD and validate this system for future discovery of novel resilience-based therapeutics.
Notably, the translational relevance of compounds will be critically evaluated in vivo and by cross-species
analyses that we and others developed using a variety of genetic, omics and clinical data. Our long-term goal
is to develop personalized in vitro 3D assays to study, quantitatively and mechanistically, how aging changes
cellular resiliency across a broad range of neuropathologies to develop novel, targeted interventions to
enhance cognitive health across a broad spectrum of neurodegenerative diseases for diverse populations,
leveraging our partnerships with pharmaceutical companies such as Icagen.

## Key facts

- **NIH application ID:** 10353296
- **Project number:** 1R21AG075496-01
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** CATHERINE COOK KACZOROWSKI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $259,650
- **Award type:** 1
- **Project period:** 2022-07-01 → 2023-03-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353296

## Citation

> US National Institutes of Health, RePORTER application 10353296, 3D Brain Tissue System for Modeling Resilience to Alzheimer's Disease and Drug Discovery (1R21AG075496-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10353296. Licensed CC0.

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