Nature: The root cause of Alzheimer's disease is... Microbial infection?

Behind the awards is a decades-long debate about the causes of Alzheimer's disease.
the mainstream theory of previous years, the root cause of Alzheimer's disease is amyloid deposition.
in clinical trials, the vast majority of drugs targeting amyloid deposition have failed.
these drugs not designed to be in place? Or is the amyloid theory fundamentally wrong? While amyloid theory is constantly being challenged, alzheimer's disease "infection theory" has gradually received people's attention.
theory that Alzheimer's disease is rooted in microbial infections, and more and more evidence is available.
, the journal Nature published a lengthy report detailing the topic.
two theories, microbial infection theory sounds like a perverse theory.
the theory of amyloid seems to be correct - it's all in the brains of Alzheimer's patients, and the way it's produced is clear.
if these amyloid proteins are not removed in time, they further induce an inflammatory response that causes tau protein entanglements that eventually damage and kill neurons.
with this theory, the severity of Alzheimer's disease appears to be positively related to the density of tau protein entanglements.
other genetic evidence is also bullish on amyloid theory.
that there are specific genetic variants that significantly increase the risk of Alzheimer's disease, which can affect people as early as the age of 30-60.
these genetic mutations affect the pathogenesus associated with amyloid proteins, or the inflammatory response in the brain.
, these phenomena are well explained by amyloid theory.
but some scientists have pointed to doubts, such as the fact that many people don't have Alzheimer's disease and still have amyloid deposits in their brains.
the presence of these heterogeneic amyloid protein deposits, consistent with microbial infection theory.
fact, microbial infection theory is not a substitute for amyloid theory, but more of a supplement.
the theory that amyloid is not just a poisonous molecule, but it has an important role to play: clearing the brain of infections.
normal, these proteins will "do things to brush off, deep in merit and name."
age or genetic factors can break the balance of the system, accumulate too much amyloid, and cause problems.
scientists did find traces of microbes in the brain samples of many Alzheimer's patients.
evidence only suggests a link between microbes and Alzheimer's disease, and does not mean they are involved in the disease.
recent papers have made us pay more attention to microorganisms.
A 2018 study published in the journal Neuron, published in Cell, used big data to explore whether there was consistent gene expression in brain samples of Alzheimer's patients and healthy people, and found that many changes in gene expression appeared to be linked to viral infections.
further analysis showed that the levels of human herpes virus (HHV) 6A and 7 increased significantly in patient brain samples and could affect the expression of the classic "Alzheimer's gene" such as BACE1, PSEN1, and APBB2.
2019, a study published in Science Advances, a sub-journal of science, found that in the brains of Alzheimer's patients, there is a large amount of Porphyromonas monocytobacteria and the toxins it secretes that cause periodontitis.
, mice infected with the bacteria had more β amyloid protein in their brains and more frequent lesions in their brains.
these findings have not become a "real hammer" for microbial infection theory, but have caused more heated debate.
For example, some virologists can't repeat the findings of the Neuron journal, while others point out that there may be problems with the source of samples from these Alzheimer's patients, who had a pre-death health condition, incomplete protection of brain tissue, and microbes that could easily invade.
there are also too many uncertainties in our research on Science Advances.
large-scale research may be the only way to better shed light on the relationship between microbes and Alzheimer's disease.
2018, scientists in Taiwan published the results of a long-term, large-scale study that found that more than 30,000 people infected with the herpes virus were 2.6 times more likely to develop alzheimer's disease in old age.
in groups using antiviral drugs, the risk was reduced by 90 per cent.
2017, a team at Columbia University began evaluating whether the antiviral drug valacyclovir could delay mental decline and amyloid deposition in patients with mild Alzheimer's disease.
the study is expected to be available in 2022.
's future is a good idea in a long story in Nature - so far, no one has thought carefully about whether β amyloid itself has a special effect.
the logic behind this is clear: in different species, the sequence is highly conservative and at least 4 million years old.
Rudolph Tanzi, a neurogeneticist at Massachusetts General Hospital (MGH), asked his students to test β bactericidal ability of amyloid protein.
in test tubes, the protein is effective in killing Streptococcus pneumoniae and E. coli, similar to known antimicrobial peptides.
fact, these antimicrobial peptides β similar lengths and properties to these amyloid proteins.
professor Rudolph Tanzi (Picture: MGH), they also conducted a mouse experiment in which they injected salmonella typhoid salmonella into their brains.
study showed that mice that produced amyloid deposits lived longer than mice that did not produce amyloid deposits.
, amyloid protein also acts as an antimicrobial.
in two cases, sticky amyloid proteins were interwoven into a web that wrapped pathogens.
researchers also observed that amyloid deposits were produced more quickly in mice and cultured cells after exposure to the virus.
these results are encouraging, but they are far from the last key evidence of a series of signal-level connections that have been shown to cause Alzheimer's disease.
but scientists are also actively searching for evidence.
A paper published in Nature in September by Professor Li Yuming of memorial Sloan-Kettering Cancer Center suggests that when the virus enters the brain, it activates a protein called IFITM3, which regulates the activity of γ secretion enzymes and promotes the production of amyloid proteins.
the first time scientists have found that an immune response promotes the production of this key pathological protein.
as more evidence emerges, perhaps we can have a clearer understanding and understanding of the causes of Alzheimer's disease.
this will not only guide the development of more accurate and effective drugs, but will also change our philosophy of treating Alzheimer's disease - will inhibit amyloid deposits and make the brain powerless to fight infection? Of course, all this is based on theoretical speculation.
even the most optimistic supporters cannot say that microbial infections are the culprits of Alzheimer's disease.
that evidence that germs cause Alzheimer's disease is "the most difficult to provide."
other scientists say they are happy to bet five pounds on the theory.
if you put the bet up to 500 pounds, it's better to keep watching.
resources: .1? Are are the seedings of some cases of Alzheimer's disease? Retrieved November 4, 2020, from [2] Hur, J., Frost, G.R., Wu, X. et al. (2020) The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer’s disease. Nature.[3] Stephen S. Dominy et al., (2019) Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors, Science Advances, DOI: 10.1126/sciadv.aau3333 [4] Ben Readhead et al., (2018), Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus, Neuron, DOI: 10.1016/j.neuron.2018.05.023