Have you brushed your teeth properly? New research suggests that oral diseases can trigger Alzheimer's disease

This article is the original of the translational medicine network, please indicate the source when reprinting

Author: Jevin

Alzheimer's disease (AD) is a neurodegenerative disease that is one of the biggest mysteries in
the medical community.
With the increasing trend of population aging, the incidence of AD continues to increase and has become the fifth leading cause of death in
the world.
Alzheimer's disease accounts for about 70%
of these cases.
However, the pathogenesis
has not yet been found.
In recent years, more and more scientists have confirmed that there are multiple populations of oral pathogenic microorganisms in the brains of Alzheimer's patients, and the reduction of these microbial populations can effectively alleviate the course
of Alzheimer's disease.

Recently, researchers reported the link between gum disease and Alzheimer's disease in the Journal of Alzheimer's Disease, and made new discoveries
about the interaction of ganga porphyrin monas with two important pathological lesions in the brains of Alzheimer's patients, namely β amyloid plaque (Aβ) and Tau protein hyperphosphorylation caused by neurofibrillary tangles.

https://pubmed.
ncbi.
nlm.
nih.
gov/36031895/

Porphyrin gingival

 01 

Porphyrin gingivum is a non-fermented sugar-negative anaerobic bacillus and is one of
the most extensively studied and well-documented periodontal pathogens.
It destroys the structure around the tooth by producing multiple virulence factors and extracellular proteases, ultimately leading to tooth loss
.
In addition, cytokines released by Porphyrin monas gum will reach the whole body with blood circulation, causing cardiovascular disease, insulin resistance and other systemic diseases, mainly through immune response pathways and non-immune response pathways
.

Immune response pathway: It was found that Ganga gum can release the pro-inflammatory factors TNF-α, IL-6 and IL-1β, activating the inflammatory response, thereby causing cognitive deficits
in middle-aged mice.
An immune response occurs in the brain after being infected by an oral pathogen, and in the central nervous system, this immune response belongs to the classic pathway
dominated by complement activation.
The complement-mediated immune response increases the susceptibility of neurons and promotes the synthesis of complement proteins by microglia
.
In addition, Porphyrin gingiva has a temporal cumulative effect
on damage to neurons in the brain.

Non-immune response pathway: The researchers used a mouse model to infect Porphyromonas gum within 24 weeks, which was subsequently found in hippocampal neurons
.
This phenomenon suggests that bacteria play a direct role in parenchymal infections of the brain, rather than long-range effects
mediated by inflammatory factors.
In addition, Gangerphyrin monas gum may cause neuroinflammation and neurodegeneration, microglia and astrocyte proliferation, and the formation of pathological features
such as intracellular amyloid plaques and nerve fiber tangles.

In addition, LPS, one of the main virulence factors of Porphyrin monas gingiva, regulates the expression of amyloid precursor proteins in the brain, causing Aβ to deposition in neurons and promoting the development
of AD.
Studies have found that the gingival protease secreted by Porphyrin gingivum has a variety of effects such as helping bacteria colonize, suppressing the host immune system, and destroying tissue stability, and is cytotoxic
.
The researchers found in 50 brain samples of AD deaths that more than 90 percent of the samples had the presence
of gum proteases.
The mutant bacteria are constructed after knocking out the gingival protease-coding gene of Porphyromonas gum, and then the mouse oral cavity
is infected with this mutant.
The results showed that compared with the mice infected with normal strains, the pathogenic bacteria in the brains of mice infected with mutant strains were significantly reduced, and Aβ deposition was also significantly reduced
.

Tau protein tangles with gum protease

 02

Tau protein is a tubulin that maintains the stability
of axonal microtubules.
Studies have shown that phosphorylated Tau peptide A exists in aqueous solution β flake structure, has a certain antibacterial properties, and can significantly inhibit the activity
of porphyrin monas gingival.
This may be associated with a decrease in PH in the phosphorylated Tau protein, while Porphyrin gingiva is sensitive to pH and is only suitable for survival
in 6.
5-7.
0.

However, hyperphosphorylation causes Tau proteins to dissociate from microtubules, and free Tau proteins are virulent and difficult to dissolve
.
The microtubule domain of its specific binding collapses, which in turn destroys the cytoskeleton of neurons and reduces the ability
of neurogen transport systems.
Free Tau proteins in neuronal cell bodies can be transformed into pairs of spiral filaments or straight filaments that form nerve fiber tangles
.

Subsequently, researchers in vitro tests proved that gingival proteases have the function
of cutting tau proteins into pieces.
This suggests that the tau protein tangles that appear in the brains of AD patients are most likely caused
by gum proteases.

Gum disease and Alheimer's disease

 03 

The latest studies have shown that the values of LPS and gingival protease in the brains of Alzheimer's patients are significantly elevated, and some lipopolysaccharides are present in the form of epithetic vesicles, carrying some gingival proteases and weaker virulence factors
.
When the mouth is infected with Porphyrin monas gum, the brain also undergoes neuropathological changes
associated with Alzheimer's disease.

After transmission electron microscopy analysis of 7 non-phosphorylated Tau proteins and 3 phosphorylated Tau proteins, the secondary and tertiary structures of non-phosphorylated peptide B showed less spiral distortion, while peptide C showed significantly more spiral distortion along the entire fiber length after phosphorylation, which was easy to self-aggregation and the formation of paired spiral fibres
on the tertiary structure.
Further aggregation of paired spiral filaments will lead to the formation of nerve fiber tangles, which in turn can lead to Alzheimer's disease
.

Gum disease is inextricably linked
to Alheimer's disease.
After oral infection with pathogenic bacteria, patients can be susceptible to Alzheimer's disease, therefore, good oral hygiene management will help prevent the occurrence
of Alzheimer's disease.

Resources:

https://pubmed.
ncbi.
nlm.
nih.
gov/36031895/

Note: This article is intended to introduce medical research advances and cannot be used as a reference for
treatment options.
For health guidance, please visit a regular hospital
.

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