# Infection-driven mechanisms associated with Alzheimer's disease pathology

> **NIH NIH RF1** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $1,952,526

## Abstract

ABSTRACT
 It is suggested that infections increase the risk for Alzheimer's disease (AD). However, the evidence
behind this is not well described. Infections, infectious agents, and their toxic products are associated with short-
and long -term cognitive decline and neurodegeneration. Potential links between infections and AD include the
activation of the peripheral immune system, the increase in the permeability of the blood-brain barrier, the
production of inflammatory mediators, and the presence of peripheral immune cells in the brain triggering a
severe glial cell activation, among others. Imbalance of the immune system also increase the synthesis and
accumulation of the amyloid-beta (Aβ) peptide, the hyperphosphorylation of tau, and the induction of chronic
inflammation in the brain. The main goal of this project is to investigate the role of peripheral and brain infections
in the development of AD. Our aims are to study the role of sepsis and meningitis in brain amyloid and tau
pathology, associated cognitive decline, and brain inflammation. We expect that outcomes from this project will
help us to identify and understand the molecular and cellular mechanisms underlying the role of infection in the
pathogenesis of AD. For this purpose, we will use a series of established and novel biochemical assays in animal
models of AD and human-derived samples. Mouse models of brain Aβ and tau accumulation will be subjected
to peripheral infection through cecal ligation and perforation (CLP) surgery, or to bacteria administration into the
cisterna magna to induce meningitis. Then, we will assess whether these infection modalities trigger, accelerate,
or worsen AD pathology. The participation of the peripheral immune system in these events will be explored by
bone marrow transplants from non-AD mice subjected to infection to naïve AD mouse models. Clinically, we will
test for the presence of disease-associated Aβ and tau in the blood of septic and post-septic patients and the
cerebrospinal fluid (CSF) of individuals afflicted by meningitis. This project will provide us with valuable insights
into events associated with AD risk and will produce critical data for understanding the role of the immune system
in dementia. Clinically, this research may help identify individuals with an increased risk for developing AD.

## Key facts

- **NIH application ID:** 10214054
- **Project number:** 1RF1AG072491-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Tatiana Barichello
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,952,526
- **Award type:** 1
- **Project period:** 2021-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214054

## Citation

> US National Institutes of Health, RePORTER application 10214054, Infection-driven mechanisms associated with Alzheimer's disease pathology (1RF1AG072491-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10214054. Licensed CC0.

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