Nat commun: Alzheimer's disease pathological protein is related to cell death in mice

June 11, 2019 / BIOON / - a new protein related to Alzheimer's disease (AD) has been found by researchers at the brain science center (RIKEN CBS) of the Japanese Institute of physics and chemistry Capon may promote the connection between amyloid plaques and tau pathology, the two most famous culprits of AD, and their interaction will lead to brain cell death and dementia symptoms The latest findings come from the takaomi Saido team of RIKEN CBS, who used a novel mouse AD model, the study published in the journal Nature communications Ad is a complex disease, whose destructive conditions are β - amyloid plaques and neurofibrillar tangles in the brain, also known as tau pathology To study the link between these features, the team identified Capon, a protein that binds to tau proteins The Capon gene is a known risk for other mental disorders, because AD may be accompanied by mental symptoms, and the team speculated that Capon may form a link between these symptoms In fact, when they studied a type of AD mice, they found Capon accumulated in the hippocampus, an important memory center in the brain In addition, the accumulation of CAPON was more serious when the pathological characteristics of β - amyloid plaque appeared Photo source: nature communications used a new app / MAPT double tap process to create another type of mouse AD model, and the team inserted Capon DNA into the brain, resulting in over expression of CAPON These mice showed obvious neurodegeneration, increased tau protein level and atrophy of hippocampus "This means that accumulation of CAPON increases the pathology associated with AD," said Shoko Hashimoto, lead author of the study and of RIKEN CBS "Although Capon induced cell death can occur in many different ways, we believe that this protein is a promoter between neuroinflammation and tau pathology "This is the first study to use app / MAPT double knockin mice, which are designed to have human like MAPT and app genes containing pathogenic mutations If the accumulation of CAPON aggravates the pathology of AD, the team concluded that the lack of CAPON may have the opposite effect In this test, the team knocked out Capon of another ad model mice, and the pathological level of tau protein in the model mice increased significantly They found that Capon deficiency resulted in fewer tau and beta amyloid proteins, less neurasthenia, and less brain atrophy Therefore, reducing Capon level of AD mice effectively alleviated many physiological symptoms of AD "Neurodegeneration is complex, but we think Capon is an important regulator between β - amyloid, tau and cell death "Cutting this connection with drugs is a promising way to treat AD," Saido said "The app / MAPT double knockout mice developed in our lab are an improved tool in the whole research field of Alzheimer's disease "Reference: Shoko Hashimoto et al Tau binding protein Capon introduces tau aggregation and neurodegeneration, nature communications (2019) Doi: 10.1038/s41467-019-10278-x