A Protein Related to Alzheimer's Disease Reveals the Link of Plaques in Cell Death in Mice

A new protein associated with Alzheimer's disease has been identified by researchers from the RIKEN Center for Brain Science (CBS). CAPON can shed light on the link between two Alzheimer's culprits, amyloid plaques and tau pathology, whose interactions are well known to cause dementia symptoms and brain cell death. These latest findings from the Takaomi Saido group from RIKEN CBS use a new Alzheimer's mouse model.

Alzheimer's disease; It is a complex and devastating disease characterized by the formation of amyloid-ß plaques and neurofibrillary tangles, also known as tau pathology, in the brain. Examining the link between these phenomena, the research team identified CAPON, a protein that binds to tau. The CAPON gene is known to be a risk for other psychiatric illnesses, and since Alzheimer's can accompany other psychiatric symptoms, the team predicts that the CAPON gene may be linked to these conditions. Indeed, when they examined mice with one type of Alzheimer's; They found that CAPON accumulated in the hippocampus, an important memory center in the brain. Moreover, CAPON accumulation was much greater in cases of amyloid-ß pathology.

In another Alzheimer's mouse model they created using a new App / MAPT double hit process, the team implanted CAPON DNA into the brain. This caused CAPON to express excessively. These mice showed significant neurodegeneration, high amounts of tau, and shrinkage of their hippocampuses. Lead researcher Shoko Hashimoto of RIKEN CBS says; “According to the possible result, the increase in CAPON accumulation triggers Alzheimer's related pathology. Even though cell death caused by CAPON occurs through many different pathways, we think that this protein is definitely a facilitating factor between neuroiminflammation and tau pathology. "

This is the first study to use the App / MAPT double hit in mice designed to have human-like MAPTs and App genes with pathogenic mutations.

If the CAPON accumulation triggered Alzheimer's pathology, the team thought that CAPON deficiency could have the opposite effect. To test this, they eliminated CAPON in another Alzheimer's model mouse, typically with increased tau pathology. They found that CAPON deficiency caused less tau, less amyloid-ß, less neurodegeneration, and less atrophy in the brain. Therefore, reducing the CAPON level in mice with Alzheimer's effectively reduced many physiological symptoms of Alzheimer's.

Saido continues as follows; “Neurodegeneration is a complex process, but we think that CAPON is an important mediator of amyloid-ß plaques, tau, and cell death. Breaking this link with drugs is a promising method to treat Alzheimer's. The App / MAPT double shot mice developed in our lab are an advanced tool in the field of Alzheimer's research. ”

The study has been published in Nature Communications.

Source: Sciencedaily

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