# Infection as a risk factor for dementia: the role of CD36

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $386,166

## Abstract

PROJECT ABSTRACT
This proposal describes an Alzheimer's focused supplement to an R01 studying host control mechanisms
against Klebsiella pneumoniae infection. The number of people living with Alzheimer's dementia in the United
States is estimated at 5.8 million in 2020, and this number is expected to double by 2040. The role of infection
in Alzheimer's dementia pathogenesis remains unclear, however, survivors of sepsis (severe infections)
experience new cognitive deficits that persist for months to years after the inciting insult. The mechanisms
underlying cognitive deficits after sepsis are unclear. In this proposal, we plan to study the role of the scavenger
receptor CD36 in mediating cognitive decline and Alzheimer's dementia pathogenesis in septic mouse models.
Our prior studies have focused on the host response following intrapulmonary Klebsiella pneumoniae infection
where CD36 improves macrophage phagocytic function, reduces bacterial burden, and increases survival. In
contrast to its beneficial effects in the host response, CD36 may be pathogenic in Alzheimer's dementia. The
binding of CD36 to amyloid beta protein induces neuroinflammation and microglial cell activation leading to
cognitive deficits in preclinical models. Furthermore, CD36 is increased in the brains of patient's with Alzheimer's
dementia compared to age matched controls, and CD36 genetic polymorphisms are associated with increased
risk of Alzheimer's disease. We hypothesize that while CD36 is beneficial in the host response to infection, CD36
activation during sepsis induces persistent neuroinflammation and contributes to cognitive decline thereby
accelerating time to dementia, particularly in the setting of pre-existing amyloid beta deposits. We will test this
hypothesis in an antibiotic-treated mouse model of long-term survival from intrapulmonary Klebsiella
pneumoniae infection. We will examine the role of CD36 on microglial activation, cytokine and chemokine
expression, amyloid deposition, reactive oxygen species generation, and development of cognitive deficits
following sepsis using male and female C57BL/6J and CD36 -/- mice strains. In addition, we will perform studies
in aged mice and in mice with an accelerated Alzheimer's dementia phenotype (AppNL-G-F) to model the effects
of sepsis on older patients and on patients with predisposition to cognitive deficits. This proposal will be
conducted by a multidisciplinary team at the University of Pittsburgh with expertise in host response to infection,
cognitive deficits after sepsis, and Alzheimer's dementia, and will provide the foundation for future research
focused on understanding relationships between infection and dementia, and preventing cognitive decline.

## Key facts

- **NIH application ID:** 10118704
- **Project number:** 3R01HL142084-03S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Janet Sojung Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,166
- **Award type:** 3
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118704

## Citation

> US National Institutes of Health, RePORTER application 10118704, Infection as a risk factor for dementia: the role of CD36 (3R01HL142084-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10118704. Licensed CC0.

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