# Role of Periodontitis and Metabolic Syndrome Interaction in Alzheimer's Disease

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $376,250

## Abstract

Project Summary/Abstract
 A large number of studies have provided strong evidence that either periodontitis or metabolic
syndrome (MetS) increases risk of Alzheimer’s disease (AD). Given that periodontitis, MetS and AD are all
age-related diseases and the prevalence of periodontitis, MetS and AD increases with age, it is likely that
periodontitis and MetS coexist in the elderly AD patients. Therefore, it is important to investigate the role of
interactive periodontitis and MetS in the pathogenesis of AD. However, no study has been conducted to
appraise the impact of the coexistence of periodontitis and MetS on AD.
 It is known that MetS aggravates periodontitis by increasing systemic and periodontal inflammation.
Our lab is the first one to demonstrate that MetS exacerbates periodontitis by increasing systemic and
periodontal inflammation in animal models. Thus, we postulated that the interaction between periodontitis and
MetS may also aggravate AD by increasing inflammation in the brain. Furthermore, our previous studies
showed that acid sphingomyelinase (ASMase)-dependent ceramide production plays an important role in the
synergistic stimulation of proinflammatory cytokine expression in macrophages by periodontitis-related
lipopolysaccharide (LPS) and MetS-related saturated fatty acid (SFA). Based on these findings, we postulated
that ASMase-dependent ceramide production also plays an important role in the exacerbation of AD by
comorbidity of periodontitis and MetS.
 In this study, we proposed two specific aims: 1. To determine the role of the interaction between P.
gingivalis-induced periodontitis and high-fat diet (HFD)-induced MetS in the AD progression in mouse models.
We hypothesized that P. gingivalis-induced periodontitis and HFD-induced MetS cooperatively exacerbate AD
in animal models via ASMase-ceramide pathway-related inflammation. 2. To determine the effect of the
interaction between P. gingivalis LPS and SFA on inflammatory response of microglia in vitro and the role of
ASMase-ceramide pathway in this interaction. We hypothesized that P. gingivalis LPS and SFAs exert a
synergistic upregulation of proinflammatory cytokines in microglia and that ASMase-mediated sphingolipid
metabolism plays a key role in the synergism.
 In this research project, we will conduct both animal studies using AD models and in vitro studies using
microglial cells to test our hypothesis. We will employ biochemistry, immunology, cellular and molecular
biology techniques to elucidate the underlying mechanisms. We believe that this collaborative study supported
by Alzheimer’s-focused administrative supplement will yield novel insights into the pathogenesis of AD. More
importantly, this study will facilitate the multidisciplinary collaboration between Dr. Huang and Dr. Bhat and
help developing a collaborative research program on AD at MUSC.

## Key facts

- **NIH application ID:** 10123158
- **Project number:** 3R01DE027070-03S1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Yan Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,250
- **Award type:** 3
- **Project period:** 2020-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123158

## Citation

> US National Institutes of Health, RePORTER application 10123158, Role of Periodontitis and Metabolic Syndrome Interaction in Alzheimer's Disease (3R01DE027070-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10123158. Licensed CC0.

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