# A Systems Approach to Targeting Innate Immunity in AD

> **NIH NIH U01** · MAYO CLINIC  JACKSONVILLE · 2022 · $391,250

## Abstract

Summary:
This proposal is for an administrative supplement to our existing grant on “A Systems Approach to Targeting
Innate Immunity in AD.” We seek support for the harmonized processing and integrated analysis of genomic
(GWAS/WES/WGS) and transcriptomic (bulk tissue RNAseq and sc/snRNAseq) data from multiple AMP-
programs: AMP-AD, AMP-PD, AMP-RA/SLE and AMP-T2D. The overall goal is to provide novel insights into the
role of the immune system in Alzheimer’s disease (AD) and to contribute to ongoing efforts aimed at identifying
novel therapeutic targets. We have been members of the AMP-AD consortium since 2013 and have an in-depth
knowledge of the available datasets hosted within the AD-knowledge portal. We have generated and contributed
data under multiple studies, including Mayo RNAseq, MC-CAA, MCADGS, MCSA and TAUAPPms and have a
thorough understanding of the data sharing process. We are/have also been leading and contributing members
for multiple working groups within the AMP-AD consortium, affording us familiarity with the data hosted within
the portal and the necessary experience in working with big-datasets. A major focus of our prior and ongoing
work within AMP-AD is the role of the immune system in AD. In this proposal we aim to expand these efforts to
investigate and identify immune signatures that are associated with AD and related disorders and comorbidities
including Parkinson’s disease (PD), Type-2-diabetes (T2D), and immune disorders such as rheumatoid arthritis
(RA) and lupus (SLE). To accomplish these goals we have three aims that will likewise contribute to the broader
aims of the parent U01 and the consortium goal of accelerating the identification of novel therapies for AD. In
Aim 1 our goal is to identify genetic variants and transcriptional networks in inflammatory pathways that are
shared between as well as distinct for diseases and aging. The central hypothesis of this aim is that there are
aspects of the immune system that interact with the aging process and are dysfunctional in disease, some of
which will cause broader systemic disease while others may be specific to AD. Defining the aspects of immune
dysfunction that contribute to AD more specifically and in the context of aging is expected to address this key
knowledge gap. In Aim 2 we plan to discover inflammatory signatures that are shared between as well as tissue-
specific. While AD is a neurodegenerative disease, identification of immune changes in peripheral tissues (eg.
blood and kidney) that either reflect CNS changes, disease pathophysiology, or systemic immune dysfunction
can have implications for furthering understanding of underlying disease etiology and have biomarker potential.
In Aim 3 we will expand our analysis to determine inflammatory cell-subtype proportion and cell-specific
molecular signature perturbations in disease and aging. While bulk tissue studies have provided key insights into
disease such as immune activation and myelin depletion, they la...

## Key facts

- **NIH application ID:** 10506095
- **Project number:** 3U01AG046139-09S1
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** NILUFER ERTEKIN-TANER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $391,250
- **Award type:** 3
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10506095

## Citation

> US National Institutes of Health, RePORTER application 10506095, A Systems Approach to Targeting Innate Immunity in AD (3U01AG046139-09S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10506095. Licensed CC0.

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