# Identification of the genetic and transcriptomic networks of cognitive and neuropathological resilience to AlzheimerÃ¢ÂÂs disease associated viruses

> **NIH NIH U01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2021 · $1,163,147

## Abstract

ABSTRACT
Investigators have long suspected that pathogenic microbes might contribute to the onset or progression of
Alzheimer's disease (AD) although findings have been inconclusive, with reports of microbe-related antigens
from entities as diverse as herpesviruses and borrelia species. Recent large-scale efforts such as the NIH
Accelerating Medicines Partnership for Alzheimer's disease (AMP-AD) are generating multiple forms of next-
generation sequencing data on large, well-characterized AD cohorts and controls. These data present new
opportunities to detect the presence of viral species directly from clinical samples and to put measures of viral
species abundance into the context of the most molecular networks and clinical features. We plan to build upon
our preliminary work that has identified consistently increased abundance of specific Herpesviridae species in
post mortem brain tissue from individuals with AD, and demonstrated viral regulation of AD associated molecular,
genetic and clinic-pathological networks. The Aims of this proposal are designed to illuminate the genetic,
transcriptomic and proteomic host networks that confer cognitive and neuropathological resilience to these AD-
associated viral species, with the goal of identifying novel therapeutic opportunities for the treatment of AD. This
requires that we systematically characterize the impact of viral perturbations that are known or suspected to
associate with a diagnosis of AD, amyloid plaque density, neurofibrillary tangle severity or clinical dementia
ratings, and identify the host networks capable of modifying these relationships. By modelling the causal
interactions that relate virus, host and disease, we can conceptualize these host molecules (and their appropriate
perturbations) as potential mediators of resilience in the face of viral infection. We will validate genetic and small
molecule perturbations of virally infected cerebral organoids systems, monitoring changes in resilience to viral
infectivity, AD associated neuropathology markers, and host transcriptomics, including activity of targeted
resilience networks. The expected outcome of this study is to identify and evaluate specific host molecular
networks and small molecules that are capable of modulating host responses to infection with AD-relevant
viruses.

## Key facts

- **NIH application ID:** 10221574
- **Project number:** 5U01AG061835-04
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Benjamin Readhead
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,163,147
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221574

## Citation

> US National Institutes of Health, RePORTER application 10221574, Identification of the genetic and transcriptomic networks of cognitive and neuropathological resilience to AlzheimerÃ¢ÂÂs disease associated viruses (5U01AG061835-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10221574. Licensed CC0.

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