# Targeting IDO in SARS-CoV2-induced Alzheimer's Disease progression

> **NIH NIH R56** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2022 · $400,000

## Abstract

Project Summary/Abstract
Alzheimer’s disease (AD) is a national health crisis, affecting many Americans with total annual payments
projected to be more than $1 trillion by 2050. The risk for Alzheimer’s disease (AD) is an interaction between
inherited and environmental risk factors that, with age, drives pathology resulting in neurodegeneration and
disease onset. Increasing epidemiological evidence indicates that ~80% of individuals infected with SARS-CoV2,
and who develop Covid-19, experience neurological sequelae characterized by common etiological factors of
Alzheimer’s disease, including cognitive and neuropsychiatric deficits. Therefore, there is a strong possibility in
SARS-CoV2 causation of neurological conditions, such as Alzheimer’s disease, based on the biology and host
immune responses to the virus. Biological factors intertwined with the overactivity of the CNS
inflammatory response during Covid-19, impact the functional status of the CNS. For example, the bidirectional
relationship between CNS inflammation and dysregulation of the kynurenine (KYN) pathway (KP) and its
metabolites, such as kynurenic acid (KYNA) and quinolinic acid (QUIN), are found in the blood and cerebrospinal
fluid of AD patients; and levels are correlated to severity of neurological and cognitive impairments associated
with viral infections such as HIV. Importantly, disruption and dysregulation of KP metabolites in Covid-19 patients
is correlated to disease severity and triggered by inflammation-induced indoleamine 2,3-dioxygenase (IDO). This
indicates that dysregulation of critical KP metabolites and CNS inflammation by SARs-CoV2 may underlie
maladaptive changes in the CNS that exacerbate the development of AD. Therefore, it is critical to elucidate the
interplay between SARS-CoV2-induced KP dysregulation and CNS inflammation during Covid-19 and the
impact on AD disease progression and neuropathogenesis. The long-term goal of this proposal is to
investigate the infectious disease risk factors and mechanisms underlying the neuropathogenesis
of AD during the progression of SARS-CoV2 neurological sequelae. Using mouse-adapted SARS-CoV2, we will
address our overall objective: to delineate KP dysregulation during SARS-CoV2 CNS infection and progression
of Alzheimer’s neuropathology and neurocognitive decline correlative to CNS immune responses and
encephalitic infection. The central hypothesis is that SARS-CoV2 is a significant risk factor for the onset and
severity of AD, by triggering IDO activity thereby dysregulating KP metabolites in the periphery and CNS and
exacerbating the subsequent cytokine storm to exacerbate AD neuropathology. To address this hypothesis, we
will 1) distinguish AD-related cognitive decline exacerbated following SARS-CoV2 infection, 2) delineate SARS-
CoV2 neuropathology, disease burden, and dual activation of host immunity and KP signaling in AD, and 3)
elucidate specific IDO contributions in SARs-CoV2-mediated exacerbation of AD onset and ...

## Key facts

- **NIH application ID:** 10670498
- **Project number:** 1R56AG079190-01
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Irma Cisneros
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10670498

## Citation

> US National Institutes of Health, RePORTER application 10670498, Targeting IDO in SARS-CoV2-induced Alzheimer's Disease progression (1R56AG079190-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10670498. Licensed CC0.

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