Tuesday, August 9, 2022

Study found link between Periodontitis and Alzheimer’s Disease

Your mouth truly is the gateway to your body

Alzheimer’s disease is a neuropathological disorder causing memory loss and cognitive impairment hence degeneration of brain tissue due to inflammation and other risk factors. Alzheimer’s disease is the most common form of dementia in old age.

Periodontal disease correlates with Alzheimer’s disease!

Infection in gums which can affect the overall health of gums and jawbone, can lead to periodontitis. Periodontal disease is mainly caused by poor oral hygiene, which is responsible for tooth loss. The bacteria causing periodontal disease is Fusobacterium nucleatum (F. nucleatum). It is Gram-negative and anaerobic oral bacterium.

New research published in the journal Frontiers in Aging Neuroscience by Tufts University scientists and colleagues put forward that F. nucleatum can also cause severe generalized inflammation, which is an indication of various systemic diseases inclusive of Type 2 diabetes and Alzheimer’s disease state, by Chen’ who is trained pathologist and professor in Department of Molecular and Chemical Biology at the School of Medicine.

According to scientists, focusing on F. nucleatum can slow the spread and progression of at least two epidemics: periodontal disease and Alzheimer’s disease.

How does the periodontal disease affect the brain?

The new research performed on mice states that F. nucleatum results in an unusual generation of microglial cells. Microglial cells are immune cell that helps prevent infection and maintain the nervous system’s overall health. This over formation of microglial cells can lead to inflammation and infection, which is determining factor for cognitive decline that will progress Alzheimer’s disease.

Pathogenesis of Alzheimer’s disease:

The important pathological indication of Alzheimer’s disease is senile plaque formation by abnormally folded beta-amyloid (A β) protein outside neurons and neurofibrillary tangles. This cause of Aβ plaques is hyperphosphorylated Tau protein inside neurons which can cause neurodegeneration in the brain. Moreover, the microbiota of the host may responsible for the formation of beta-amyloid. Oral microbiota is determining factor of periodontitis and can over cross between periodontitis and other systemic diseases. For example, Nao Yuki found that periodontitis associated with Porphyromonams gingivalis can put on the pathological characteristics of Alzheimer’s disease, which also promote the accumulation of aβ protein and aggravate cognitive impairment.

So, this all suggests that local periodontal information can excite brain tissue inflammation. Studies also found that P. gingivalis can be detected in patients with Alzheimer’s disease. But there is also a confirmed study that states that P. gingivalis is associated with Alzheimer’s disease lesions, causing neurotoxicity. Hence, gingipain inhibitor treatment is used effectively in mice that prevent bacterial infections and reduce inflammation in the nervous system.

Various experiments were performed while studying the link between periodontal and Alzheimer’s disease:

This study was performed in conformity with the policies of Tufts University. All mice used in this study were housed at the Tufts Medical Center Animal Facility (Boston, MA), fully accredited by the American Association for Accreditation of Laboratory Animal Care. The Institutional Animal Care and Use Committee (IACUC) approved all animal protocols for this study.

Co-culture of SIM-A9 cells and Fusobacterium nucleatum:

Scientists mainly focused on two noncoding RNAs: microRNA and lncRNA. MicroRNA monitors the production of proteins in cells. In contrast, the lncRNA performs other functions to regulate gene expression and could ultimately be used to treat atherosclerosis (hardening of the arteries) and periodontal disease, diabetes, cancer, and diabetic bone disease.

The research also suggests potential drug targets that could specifically quench the local and systemic inflammation caused by F. nucleatum in a periodontal environment.

The study shows that a molecule called MicroRNA-335-5P can prevent periodontal bacteria from causing harm to the gums. The molecule may also effectively destroy the harmful compounds in the brain that cause Alzheimer’s.

MicroRNA-335-5P, in particular, could target three “bad” genes—DKK1, TLR-4, and PSEN-1—all believed to be related to Alzheimer’s disease.

Chen said, “Our studies show that F. nucleatum can reduce the memory and thinking skills in mice through certain signal pathways. This is a warning sign to researchers and clinicians alike.”

“Testing for bacterial load and degree of symptoms could one day become a way to measure the effects of F. nucleatum and manage treatment to slow the progression of both periodontal disease and Alzheimer’s.”

Scientists also designed a molecule called adipoAI with strong anti-inflammatory properties. Clinical trials will determine its effectiveness in treating a range of inflammatory diseases, including Type 2 diabetes, Alzheimer’s disease, and periodontal disease.

Journal Reference

  1. Wu H, Qiu W, Zhu X, Li X, Xie Z, Carreras I, Dedeoglu A, Van Dyke T, Han YW, Karimbux N, Tu Q, Cheng L and Chen J (2022) The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways. Front. Aging Neurosci. 14:912709. DOI: 10.3389/fnagi.2022.912709
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