# Pathogenesis of Polymicrobial Cerebritis-Related Dementia

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $320,830

## Abstract

The broad, long-term objectives of my laboratory are to understand the immune and environmental basis of
inflammatory lung diseases such as asthma and the broader role of these etiologic factors in human disease.
Inexplicably, Alzheimer's disease (AD), the most common cause of dementia and the 5th leading cause of
death among elderly Americans, is epidemiologically linked to asthma, suggesting the existence of a shared
etiologic factor. AD is the only one among the top 10 causes of death that cannot be prevented, slowed, or
cured. AD is already the most expensive medical condition in the US, with total costs estimated at $200 billion,
but this is expected to rise to an astonishing $1 trillion by 2050 if improvements in medical care are not found.
Despite these alarming statistics and decades of research, the fundamental cause of AD and related
dementias remains unknown. As we have previously shown, asthma in many cases is due to airway mycosis,
a superficial infection of the airway mucosa involving diverse fungi. This discovery is the central observation in
our parent application AI135803. Furthermore, AD has been linked to polymicrobial brain infections based on
the discovery of fungi, especially the yeast Candida albicans, and a variety of bacteria in the brains of those
suffering from AD. The premise of this application is therefore that low-grade polymicrobial brain infections
involving C. albicans and bacteria potentially deriving from the gastrointestinal (GI) tract could be a root cause
of AD and potentially other chronic neurodegenerative conditions. Our preliminary studies demonstrated that C.
albicans induces canonical features of AD, providing in vivo support of the concept that fungal infection may
underlie AD in some subjects. Our additional studies now show that C. albicans when administered to mice
through the oral route escape the GI tract and enter the mouse brain together with numerous bacteria,
producing a polymicrobial, fungus-centered cerebritis. Nonetheless, definitive evidence of a fungal infectious
etiology in AD is lacking. We therefore hypothesize that GI tract infection with C. albicans spreads
hematogenously to the brain together with enteric bacteria to establish polymicrobial brain infections. To test
this hypothesis, we propose the following Aims: Aim 1. To determine the origin and identity of bacteria
associated with polymicrobial cerebral mycosis (C. albicans + bacteria). Aim 2. To determine the mechanism
by which C. albicans and bacteria establish polymicrobial brain infections. Together, these aims will elucidate
the possible contribution of environmental fungi and bacteria to the pathogenesis of polymicrobial brain
infections previously linked to AD.

## Key facts

- **NIH application ID:** 10119639
- **Project number:** 3R01AI135803-03S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** DAVID B CORRY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $320,830
- **Award type:** 3
- **Project period:** 2018-03-23 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119639

## Citation

> US National Institutes of Health, RePORTER application 10119639, Pathogenesis of Polymicrobial Cerebritis-Related Dementia (3R01AI135803-03S1). Retrieved via AI Analytics 2026-09-24 from https://api.ai-analytics.org/grant/nih/10119639. Licensed CC0.

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