The latest research progress of Alzheimer's disease

November 4, 2019 / BIOON / -- this issue brings you the latest research results related to Alzheimer's disease I hope readers will like it 1 ELife: targeted therapy for metabolic dysfunction or promising therapy for Alzheimer's disease doi: 10.7554/elife.50069 recently, a research report published in the International Journal eLife found that metabolic dysfunction is the main cause of Alzheimer's disease Alzheimer's disease is one of the most common neurodegenerative diseases affecting the elderly in the world, and it is also a common cause of dementia In Singapore, one in ten individuals aged 60 and over will suffer from dementia After more than 20 years of research, researchers still have not identified the specific cause of Alzheimer's disease, and there is no effective treatment At present, researchers have put forward two competitive theories to explain the cause of Alzheimer's disease The first theory holds that the accumulation or main inducement of a special protein called β amyloid protein in the brain; the second and recent theories hold that metabolic dysfunction, especially the abnormal function of cell mitochondria, may be the main cause of Alzheimer's disease In this study, the researchers found that before the level of β amyloid increased significantly, the patients' metabolic defects could be detected, and they could recognize these changes by using C.elegans, because C.elegans shares many similarities with human cells at the molecular level After in-depth study, the researchers found that metformin, a diabetes drug, might have It can effectively reverse these metabolic defects and restore the health and life span of nematodes   Gruber said that despite the investment of billions of dollars, the current clinical trials of Alzheimer's drugs targeting specific proteins have failed Now researchers have found a strong correlation between mitochondrial dysfunction and Alzheimer's disease pathology Therefore, by targeting metabolic defects, especially mitochondrial defects, a preventive strategy may be adopted Effectively inhibit the occurrence of Alzheimer's disease The researchers explained that metabolic and mitochondrial dysfunction may be the basic characteristics of aging in general population and patients with age-related diseases (including Alzheimer's disease); therefore, we should pay special attention to the performance of individual aging, and develop preventive and therapeutic strategies by targeting the aging mechanism rather than treating diseases after symptoms appear 2 Clin genetics: blood test can find the risk of Alzheimer's disease doi: 10.1186/s13148-019-0729-7 in a recent study, researchers found changes in blood sample markers related to Alzheimer's disease Based on a study of Finnish twins, one with Alzheimer's disease and the other with cognitive health, the researchers used the latest genome-wide method to examine whether there are differences in epigenetic markers associated with the disease in twin blood samples and how sensitive these differences are to changes in environmental factors Finally, the researchers found these differences in several different regions of the genome The degree of symptom deterioration in advanced Alzheimer's disease is affected by genetic and environmental factors, including lifestyle Different environmental factors can change the function of disease-related genes by changing their epigenetic regulation, for example, by regulating the formation of methylation by influencing the DNA controlling gene function By measuring the methylation level of DNA isolated from Finnish twin blood samples, the researchers found epigenetic markers associated with Alzheimer's disease in a number of different genomic regions One of these markers is also stronger in brain samples from people with Alzheimer's disease In addition, a study of Swedish twins confirmed the link between the marker and Alzheimer's disease The researchers observed that the strength of the markers was affected not only by the disease, but also by age, gender and APOE genotype (known to be associated with the risk of Alzheimer's disease) At present, the function of related markers of this gene is not very clear The researchers suspect that the gene product inhibits the activity of some enzymes in the brain, which in turn affects protein synthesis In previous studies in mice, the authors noted that the removal of related markers from this genomic region can cause learning and memory problems, which are also the main symptoms of Alzheimer's disease Riikka Lund, a docent professor at the University of Turku who led the research team, explained that even though the results provided new information about the molecular mechanism of Alzheimer's disease, more research was needed to determine whether the epigenetic markers found could be used for diagnosis 3 JEM: targeting brain immune cells helps to treat Alzheimer's disease doi: 10.1084/jem.20190980 tangles of a protein called tau are found in the brain of people with Alzheimer's disease and other neurodegenerative diseases In Alzheimer's disease, this kind of symptom occurs before the brain scan can see the tissue damage, and accompanied by people's forgetful symptoms Now, a new study finds that brain immune cells called microglia are activated by the accumulation of tau tangles, which establishes an important link between protein aggregation and brain damage The study, published in the Journal of experimental medicine on October 10, showed that elimination of these cells significantly reduced tau associated brain damage in mice - and that inhibition of these cells could prevent or delay the onset of human dementia In general, tau is helpful to the normal and healthy operation of brain neurons In some people, however, it can accumulate in toxic tangles that are a sign of neurodegenerative diseases such as Alzheimer's and chronic traumatic encephalopathy Holtzman and colleagues have previously shown that microglia limit the accumulation of harmful tau tangles But researchers also suspect microglia could be a double-edged sword In the later stage of the disease, once tau tangles are formed, cell attack tangles may damage nearby neurons and lead to neurodegenerative diseases To understand the role of microglia in tau driven neurodegeneration, Holtzman and his colleagues studied genetically modified mice carrying human tau mutations In general, the brain of the mice began to show tau tangles at about 6 months old and showed signs of nervous system damage at 9 months old Then, the researchers turned their attention to the ApoE gene ApoE4 has previously been shown to amplify the toxic effect of tau on neurons In response, the researchers genetically engineered mice to carry human apoE4 variants or not The experiment began at six months, and in the first three months, researchers fed some mice a compound that eliminated microglia The results showed that as long as microglia were present, the brains of mice with tau tangles and apoE high-risk genetic variants would contract severely and be damaged at 9 months old If the compound eliminated microglia, despite the presence of dangerous apoE mutations, the brain of the mice looked basically normal and healthy, without the accumulation of tau harmful substances "Microglia may lead to neurodegeneration through neuron death caused by inflammation In this case, if there is no microglia or microglia but they cannot be activated, the harmful tau will not accumulate and develop to the late stage, and the nervous system will not be damaged." The results show that microglia are the key to neurodegenerative diseases and an attractive target to prevent cognitive decline in Alzheimer's disease, chronic traumatic encephalopathy and other neurodegenerative diseases 4 Commun Biol: new research reveals that the formation of brain plaques in early Alzheimer's disease doi: 10.1038/s42003-019-0599-8 long before memory loss and other symptoms appear, Alzheimer's disease patients have pathological changes in the brain, such as accumulation of amyloid plaques Recently, a new study from MIT neuroscientists has proposed new insights into the accumulation mechanism of amyloid plates in the mouse brain The study also showed that the accumulation of amyloid protein in the relevant areas of the human brain was closely related to the deterioration of the disease "Alzheimer's is a neurodegenerative disease that eventually leads to a large number of neuron loss," said wennqin Huang, a postdoctoral fellow at Li Huei, co-author of the study By then, the symptoms will be hard to cure It will promote the development of related therapies to understand the abnormal areas of neurons in the brain in the early stage of disease " In recent years, many research groups have used positron emission tomography to track the accumulation of amyloid protein in the brain, but this new study can accurately observe the whole brain of mice for about one month The study showed that amyloid began to spread in deep brain areas such as the papillary body, lateral septum and hypothalamus, then along specific brain circuits into the hippocampus (the key area of memory) and cortex The team used the technology switch developed by Chung to label amyloid plaques and figure out the whole brain of 5xfad mice so that they can be finely imaged at different ages The team was able to see plaques first appear in the deep structure of the brain and then spread throughout the brain within six to 12 months "This study provides a basis for further study of how these brain regions and circuits dysfunction can cause symptoms of Alzheimer's disease," the authors said 5 PNAs: identification of a special protein that can effectively inhibit Alzheimer's disease doi: 10.1073/pnas.1914088116 recently, an international journal Proceedings of the National Academy of In the Research Report on sciences, researchers from the University of California have made great progress in the research of Alzheimer's disease; in this paper, researchers found that a special protein named tom-1 can effectively inhibit the occurrence of Alzheimer's disease Researcher Dean Frank Dr laferra said that for a long time, scientists have known that inflammation is the driver of Alzheimer's disease, but inflammation is also a very complex disease with many factors involved In this study, researchers conducted in-depth research on the protein tom-1, which can help regulate the key components of the body's inflammatory response Researchers are very interested in studying tom-1 Because of its low level in the brains of Alzheimer's patients and rodents, researchers are not aware of the key role of tom-1 The researchers found that reducing the level of tom-1 in the brain of the rodent model of Alzheimer's disease may increase the pathological performance of the patients, including the increase of inflammatory level and the aggravation of the cognitive problems related to the disease Restoring the level of tom-1 will reverse the above effects At the end of the day, researcher La Ferla said, you might think that tom-1 is a car system