Skip to main content

Alzheimer's disease protein links plaques to cell death in mice

A new protein involved in Alzheimer's disease (AD) has been identified by researchers at the RIKEN Center for Brain Science (CBS). CAPON may facilitate the connection between the two most well-known AD culprits, amyloid plaques and tau pathology, whose interactions cause brain cell death and symptoms of dementia. This latest finding from the Takaomi Saido group at RIKEN CBS uses a novel mouse model of AD. The study was published in Nature Communications on June 3.
Illustration of amyloid plaques on a nerve cell in Alzheimer's disease
Alzheimer's disease is a complex and devastating condition characterized by plaques of amyloid-β and neurofibrillary tangles, also known as tau pathology, in the brain. Investigating the connection between these features, the research team identified CAPON, a protein that binds to tau. The CAPON gene is a known risk for other psychiatric disorders, and because AD can be accompanied by psychiatric symptoms, the team guessed that CAPON could form a link between these conditions. Indeed, when they examined one type of AD mouse, they found accumulation of CAPON in the hippocampus, an important memory center in the brain. Furthermore, CAPON accumulation was even greater in the presence of amyloid-β pathology.
After creating another type of AD mouse model using a novel App/MAPT double knock-in process, the team inserted CAPON DNA into the brain, which resulted in CAPON overexpression. These mice exhibited significant neurodegeneration, elevated tau, and hippocampal shrinkage. "The implication is that accumulating CAPON increases AD-related pathology," says lead author Shoko Hashimoto of RIKEN CBS. "Although cell death resulting from CAPON can occur through many different pathways, we definitely think this protein is a facilitator between neuroinflammation and tau pathology." This is the first study to use App/MAPT double knock-in mice, which are engineered to have human-like MAPT and App genes containing pathogenic mutations.
If CAPON accumulation exacerbates AD pathology, the team reasoned that CAPON deficiency could have the opposite effect. For this test, the team knocked out CAPON in another type of AD model mouse that typically has increased tau pathology. They found that CAPON deficiency led to less tau, less amyloid-β, less neurodegeneration, and less brain atrophy. Thus, reducing CAPON levels in AD mice effectively reduced many of the physiological AD symptoms.
"Neurodegeneration is complex but we think CAPON is an important mediator between amyloid-β, tau, and cell death. Breaking this link with drugs is a promising avenue for treating AD," says Saido. "The App/MAPT double knock-in mice developed by our lab are an improved tool for the entire Alzheimer's research field."
Story Source:
Materials provided by RIKEN. 
Note: Content may be edited.

Comments

Post a Comment

Popular posts from this blog

Major surgery associated with small, long term decline in brain functioning

Major surgery is associated with a small long-term decline in cognitive functioning -- equivalent, on average, to less than five months of natural brain ageing, finds a study in  The BMJ  today. But the odds of substantial cognitive decline also increase after surgery -- approximately doubling -- although the likelihood of this is much lower than after admission to hospital for a medical condition, the findings show. Cognitive decline is the gradual loss of brain functioning that occurs with ageing. It often starts decades before the conventional definition of old age and accelerates with ageing and the presence of an increasing number of underlying health conditions. Certain health issues, such as stroke, can lead to a large "step change" in cognitive decline, and there have been concerns that surgery might also do this, with some patients refusing beneficial surgical procedures as a result, say the researchers. Few previous studies have looked at the potential im...
Post a Comment
Read more

Dark matter may be older than the Big Bang

Dark matter, which researchers believe make up about 80% of the universe's mass, is one of the most elusive mysteries in modern physics. What exactly it is and how it came to be is a mystery, but a new Johns Hopkins University study now suggests that dark matter may have existed before the Big Bang. The study, published August 7 in  Physical Review Letters , presents a new idea of how dark matter was born and how to identify it with astronomical observations. "The study revealed a new connection between particle physics and astronomy. If dark matter consists of new particles that were born before the Big Bang, they affect the way galaxies are distributed in the sky in a unique way. This connection may be used to reveal their identity and make conclusions about the times before the Big Bang too," says Tommi Tenkanen, a postdoctoral fellow in Physics and Astronomy at the Johns Hopkins University and the study's author. While not much is known about its origins,...
Post a Comment
Read more

Scientists challenge notion of binary sexuality with naming of new plant species

A collaborative team of scientists from the US and Australia has named a new plant species from the remote Outback. Bucknell University biology postdoctoral fellow Angela McDonnell and professor Chris Martine led the description of the plant that had confounded field biologists for decades because of the unusual fluidity of its flower form. The discovery, published in the open access journal  PhytoKeys , offers a powerful example of the diversity of sexual forms found among plants. The new species of bush tomato discovered in remote Australia provides a compelling example of the fact that sexuality among Earth's living creatures is far more diverse -- and interesting -- than many people likely realize. Bucknell University postdoctoral fellow Angela McDonnell and biology professor Chris Martine led the study following an expedition last year to relocate populations of the new plant, which were first noted by Australian botanists during the 1970s. Herbarium specimens from th...
Post a Comment
Read more