summary: New research points to the possibility that the development of the pathobiome in the brain plays a role in Alzheimer’s disease and related dementias.
Researchers studying brain samples found that brains with Alzheimer’s disease had significantly different bacterial profiles compared to brains without Alzheimer’s disease.
This suggests that a specific set of bacteria in the brain may be a predictor of Alzheimer’s disease. Additionally, these unique bacterial profiles were also found in ALS-affected brains, indicating a potential impact on other neurological diseases as well.
important facts:
- Brains affected by Alzheimer’s disease revealed a very different bacterial profile when compared to age-matched controls without Alzheimer’s disease.
- The set of bacteria identified in Alzheimer’s disease brains is also observed in ALS-affected brains, suggesting a broader neurological impact.
- Current Alzheimer’s disease research is increasingly challenging the long-held “amyloid cascade hypothesis” in favor of a new “pathogen hypothesis” that focuses on bacterial, fungal, and viral agents.
sauce: drexel university
The human microbiome contains the genetic material of over 100 trillion tiny microorganisms, including fungi, yeasts, bacteria, and even viruses, most of which hang out in our gastrointestinal tract and contribute to our health. I’m protecting it. But when a healthy microbiome imbalance, or “pathobiome,” is disrupted, health problems ranging from rheumatoid arthritis to bacterial vaginosis can occur.
New data published in this month’s journal Frontiers of Cellular and Infectious MicrobiologyA paper by researchers at Drexel School of Medicine provides further evidence that the development of a pathobiome in the brain may lead to some forms of Alzheimer’s disease and related dementias.
Dysbiosis, or microbiome imbalance, occurs when a biome becomes unhealthy due to the introduction of external pathogens or significant changes in the relative abundance of microbial species present. This dysbiosis can alter human metabolism and cause inflammation, and is associated with tissue damage seen in ulcerative colitis, rheumatoid arthritis, and many other chronic inflammatory diseases.
Drexel researchers studied 130 samples taken from 32 donated brains: 16 people with Alzheimer’s disease and 16 age-matched controls without Alzheimer’s disease. They discovered that every brain has a bacterial flora. However, Alzheimer’s disease brains showed a significantly different bacterial profile compared to age-matched brains. Control.
The research group used full-length 16s ribosomal RNA gene sequencing, a technique that can detect any bacterial species present in a sample. In the process, the researchers identified disease-specific bacterial groups in nearly every brain affected by Alzheimer’s disease, suggesting that these bacterial groups are strong predictors of the disease.
The authors detected five brain microbiomes, four of which are hypothesized to exist at different times in the evolution of brains affected by Alzheimer’s disease. The authors said that the observed Alzheimer’s microbiome is likely at a later stage, evolving to become more pathogenic as the disease progresses and being characterized as a pathobiome.
The authors argue that the brain starts with a healthy biome, but as the disease progresses, a new set of microorganisms replaces the original healthy microbiome, and eventually the Alzheimer’s disease pathobiome emerges, so the brain begins with a healthy biome. It is hypothesized that it will be replaced by
Samples from both sets of brain samples were taken from the frontal lobe, temporal lobe, and entorhinal cortex.
Based on the random distribution of the microbiome requiring delivery throughout the brain, the results were consistent with a disturbance in one or more brain networks. However, it is too early to determine whether the observed distribution pattern is due to the leaky blood-brain barrier, the brain’s glymphatic system, or synaptonemal transmission that is permissive to the bacteria. acne bacteria (Previously called this) Proprionibacterium acnes), Methylobacterium, Bacillus, Caulobacter, Delftia, Variovora Enter the brain.
The researchers noted that in Alzheimer’s brain samples, these pathogenic bacteria appeared to be overwhelmingly replaced. Comamonas sp. Bacteria associated with the brain without dementia.
“probably, Comamonas “Bacteria that are part of a healthy brain microbiome are the first sign of impending dementia,” said Dr. Garth D. Ehrlich, professor of medicine and senior author of the paper.
“We are currently coming up with questions to guide future research, but there are many hypotheses. The culprit could be a bacterium, or it could be something else, such as a fungus, parasite, or virus. Possibilities can be considered at the same time.”
When a patient develops Alzheimer’s disease, there is inflammation in the brain characterized by amyloid-beta deposits formed by increased production of Aβ peptides (antimicrobial peptides that are part of the innate immune response), leading to the formation of amyloid plaques in the brain. will be done. brain.
Similarly, Alzheimer’s disease is characterized by tangles of tau proteins found within cells characterized by aberrant phosphorylation that ultimately leads to the destruction of synapses and neurons, but is also difficult to stop the spread of the pathogen in the brain. It has also been proven to be helpful.
These protein-directed pathologies, known as the “amyloid cascade hypothesis,” have been a major focus of Alzheimer’s disease research for decades. Recent studies have suggested a role for bacteria, fungi, viruses, the immune system, and brain inflammation, which some researchers are calling the “pathogen hypothesis.”
“Multiple studies have shown that bacteria are present in brains affected by Alzheimer’s disease,” said Dr. Jeffrey Lapides, adjunct associate professor of medicine and senior author of the study.
“Possibly plaques, whose components have antibacterial properties in vitro, are not a direct cause of Alzheimer’s disease, but rather a response to bacteria in the brain, some benign and others pathogenic, and possibly cognitive They may be causing damage that is not yet functional. They are defective and they are part of the pathobiome.”
This unique set of bacteria found in brains affected by Alzheimer’s disease is also commonly found in brains affected by the neurodegenerative disease amyotrophic lateral sclerosis (ALS), and this set of bacteria has been linked to multiple neurological diseases. It has been suggested that it may contribute.
According to the authors, the next steps in this research will be to study the possible contributions of other microorganisms and to elucidate what happened physiologically in the brain to cause this microbiome to change over time. It is said that it is a thing.
“The development of Alzheimer’s disease and other dementias is complex and likely involves the interaction of many systems,” Ehrlich said.
“I believe that the more infections we have in the brain, the greater the risk of Alzheimer’s disease. There are many pathogens that can increase risk. This pathway biome is not the whole answer, but it is part of the puzzle. Department.”
Exactly where the problematic bacteria reside in the brain is also an open question, the researchers say. Researchers need to know more precisely where bacteria are located to better understand the role they play.
The authors found that when an unhealthy pathobiome is present in the frontal lobe, Alzheimer’s disease is much more likely to be present. It is less likely to occur in the temporal lobe.
Although there are many unknowns, this is an important step forward in microbiome research, the authors said.
“The strength of our study is also the combination of breakthrough sequencing technology with cutting-edge and innovative statistical approaches,” said the first author. Dr. Yves Monet, assistant professor of medicine. “Microbiome data analysis is notoriously difficult without a gold standard, and this study could make a significant contribution to the field of microbiome data analysis.”
An estimated 6.7 million Americans have Alzheimer’s disease, and that number is expected to nearly double by 2050, according to the Alzheimer’s Association. The National Institutes of Health has stepped up funding for dementia and Alzheimer’s disease research in recent years, currently dedicating $3.7 billion annually to research into diagnostics, drug development, and other possible treatments. .
Ehrlich and his colleagues are members of the Alzheimer’s Pathobiome Initiative. The initiative is a newly formed group of researchers developing a pilot study to examine infections in people with dementia and Alzheimer’s disease, with the ultimate goal of administering antibiotics to infected patients before the onset of Alzheimer’s disease. The purpose is to find out whether or not. Symptoms delay or prevent symptoms of the disease.
In addition to Ehrlich and Lapides, additional authors on the paper include first author Yves Moné, Joshua P. Earl, Jarosław E. Król, Azad Ahmed, and Bhaswati Sen. These are all from Drexel.
Funding: This research was funded by the Oscar Fisher Project, a philanthropic organization funded by Dr. James Truchard, as well as the Bill and Marion Cook Foundation and Drexel School of Medicine.
About this Alzheimer’s disease research news
author: Greg Richter
sauce: drexel university
contact: Greg Richter – Drexel University
image: Image credited to Neuroscience News
Original research: Open access.
“Evidence supporting a bacterial component in the pathogenesis of Alzheimer’s disease and the spatiotemporal development of the pathogenic microbiome in the brain” by Jeffrey Lapides et al. Frontiers of Cellular and Infectious Microbiology
abstract
Evidence supporting a bacterial component in the pathogenesis of Alzheimer’s disease and the spatiotemporal development of the pathogenic microbiome in the brain
background: Over the past few decades, increasing evidence has suggested the role of various infectious agents in the development of Alzheimer’s disease (AD). Although a variety of pathogens (viruses, bacteria, fungi) have been detected in the brains of Alzheimer’s disease patients, studies have focused on individual pathogens, and few studies have investigated the bacterial brain microbiome hypothesis. There are only a few examples. We profiled the bacterial communities present in the brains of non-demented controls and Alzheimer’s disease patients.
result: We collected postmortem samples from the brains of 32 subjects, consisting of 16 age-matched AD subjects and 16 control subjects, for a total of 130 samples from the frontal, temporal, and entorhinal cortices. To identify the bacteria, we used full-length 16S rRNA gene amplification using Pacific Biosciences sequencing technology. Bacteria were detected in the brains of both cohorts. The main bacteria are: acne bacteria (Previously Propionibacterium acnes) and 2 types each Acinetobacter and Comamonas Genus. We used a hierarchical Bayesian method to detect differences in relative abundance between Alzheimer’s disease and control groups. Due to the high abundance variance, we also adopted a new analytical approach based on the latent Dirichlet allocation algorithm used in computational linguistics. This allowed us to identify five sample classes, each revealing a distinct microbiota. When we ordered these classes in time, assuming that the samples represented infections that started at different times, we found that only the last class explained the presence or absence of Alzheimer’s disease. Ta.
Conclusion: Alzheimer’s disease-related pathogenesis of the brain microbiome appears to be based on complex polymicrobial dynamics. The temporal sequence revealed increases and decreases in resource abundance. C. acnes Pathogenicity occurs at off-peak abundance levels in association with at least one other bacterium from a range of genera including: Methylobacterium, Bacillus, caulobacter, delftiaand Variovorax. C. acnes may also be involved in competition that exceeds Comamonas These species are strongly associated with the non-demented brain microbiota, and their early destruction may be the first step in the disease. Our results are also consistent with a leaky blood-brain barrier or lymphatic network that allows bacteria, viruses, fungi, and other pathogens to enter the brain.