JEM: targeting brain immune cells helps to treat Alzheimer's disease

October 14, 2019 / biourn / -- tangles of proteins called tau are found in the brains 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 (image source: www Pixabay Com) in general, tau helps 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 Information source: targeting immune cells may be potential therapy for Alzheimer's original source: Yang Shi, Melissa manis, Justin long, kairuo Wang, Patrick M Sullivan, Javier remotina Serrano, Rosa Hoyle, David M Holtzman Microglia drive apoE dependent neurogenesis in a tauuopathy mouse model The Journal of experimental medicine, 2019; jem.20190980 DOI: 10.1084/jem.20190980