A Worse Oral Microbiome Correlates with Some Metrics Indicating Alzheimer's Risk

There has been some evidence for the oral microbiome, particularly the harmful bacterial species responsible for gingivitis, to contribute to systemic inflammation throughout the body. This in turn raises the risk of suffering from dementia, including Alzheimer's disease. The mechanisms look plausible, but the epidemiological evidence is mixed, suggesting that this is a small contribution to overall risk. Alzheimer's is a condition characterized by a long slow buildup of amyloid, and a later and more damaging aggregation of tau protein. Researchers here find that the presence of harmful microbial species in the oral microbiome correlates with a measure of amyloid aggregation, but not with tau aggregation in older patients. This suggests perhaps a contribution to the early establishment of the condition, but not to its later progression.

Alzheimer's disease is characterized by two hallmark proteins in the brain: amyloid beta, which clumps together to form plaques and is believed to be the first protein deposited in the brain as Alzheimer's develops, and tau, which builds up in nerve cells and forms tangles. "The mechanisms by which levels of brain amyloid accumulate and are associated with Alzheimer's pathology are complex and only partially understood. The present study adds support to the understanding that proinflammatory diseases disrupt the clearance of amyloid from the brain, as retention of amyloid in the brain can be estimated from cerebrospinal fluid (CSF) levels. Amyloid changes are often observed decades before tau pathology or the symptoms of Alzheimer's disease are detected."

The researchers studied 48 healthy, cognitively normal adults ages 65 and older. Participants underwent oral examinations to collect bacterial samples from under the gumline, and lumbar puncture was used to obtain CSF in order to determine the levels of amyloid beta and tau. To estimate the brain's expression of Alzheimer's proteins, the researchers looked for lower levels of amyloid beta (which translate to higher brain amyloid levels) and higher levels of tau (which reflect higher brain tangle accumulations) in the CSF.

Analyzing the bacterial DNA of the samples taken from beneath the gumline,the researchers quantified bacteria known to be harmful to oral health (e.g. Prevotella, Porphyromonas, Fretibacterium) and pro-oral health bacteria (e.g. Corynebacterium, Actinomyces, Capnocytophaga). The results showed that individuals with an imbalance in bacteria, with a ratio favoring harmful to healthy bacteria, were more likely to have the Alzheimer's signature of reduced CSF amyloid levels, indicating low clearance and greater amyloid in brain tissue. The researchers hypothesize that because high levels of healthy bacteria help maintain bacterial balance and decrease inflammation, they may be protective against Alzheimer's. The researchers did not find an association between gum bacteria and tau levels in this study, so it remains unknown whether tau lesions will develop later or if the subjects will develop the symptoms of Alzheimer's.

Link: https://www.eurekalert.org/pub_releases/2021-04/nyu-iig040721.php

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