Amyloid causes Alzheimer’s disease in more than one form ;
Most researchers believe that amyloid plaque is the culprit behind Alzheimer’s disease. They know that damages brain cells. are now finding also accumulates in the blood vessels. Learn how accumulates on the damage it causes and what to do to avoid
the results may shed some light on a common phenomenon called “mixed dementia” refers to the diagnosis of both Alzheimer’s disease and vascular dementia. This new discovery could explain why vascular dementia, caused by problems with blood flow in the brain, so it is common in people with Alzheimer’s disease.
The study, published in the online edition of the Proceedings of the National Academy of Sciences (PNAS) , is the first to identify the role the receptor of innate immunity CD36 plays in the harmful brain blood vessels and promote the accumulation of amyloid deposits in these vessels , a condition known as cerebral amyloid angiopathy (CAA) .
Importantly, the study provides the rational basis for targeting CD36 to slow or reverse some of the cognitive deficits in Alzheimer’s disease by preventing the CAA.
“Our results strongly suggest that amyloid, in addition to damage neurons, also threatens the supply of cerebral blood and increases the susceptibility of brain damage from lack of oxygen,” says principal investigator of the study Dr. Costantino Iadecola Anne Parrish Titzell professor of Neurology at Weill Cornell Medical College and director of the Research Institute for Brain and Mind at Weill Cornell Medical College and New York Presbyterian Hospital. “If we can stop the accumulation of amyloid in the blood vessels, we may be able to significantly improve cognitive function in patients with Alzheimer’s disease. In addition, we may be able to improve the effectiveness of immunotherapy amyloid, which is in clinical trials , but it has been hampered by the accumulation of amyloid in the cerebral blood vessels. ”
The growing scientific evidence shows that changes in the structure and function of brain blood vessels contribute to brain dysfunction that underlies Alzheimer’s disease, but no one has really understood how this happens so far.
In the study, the research team – which also includes researchers from the Mayo Clinic in Florida, the McLaughlin Research Institute in Montana and Rockefeller University – used mice that were genetically engineered to develop amyloid in the brain and blood vessels, but in which the CD36 receptor was removed. They demonstrated that mice lacking CD36 have less amyloid deposition in cerebral arteries (CAA), although massive accumulation of amyloid present in brain tissue (amyloid plaques).
“Surprisingly, mice lacking CD36, which is reduced only CAA, perform better on cognitive tests than do mice with CD36 intact,” says the study’s first author Dr. Laibaik Park , an assistant professor of neurology in the brain and the Research Institute of Mind.
“In essence, reduced amyloid burden in brain blood vessels, or CAA, was able to preserve cognitive function despite the accumulation of amyloid plaques in brain tissue,” says Dr. Iadecola, who is also a neurologist at NewYork-Presbyterian hospital / Weill Cornell Medical Center. “These results indicate that clear the amyloid cerebral blood vessels could be of great benefit to patients with Alzheimer’s disease. These findings are based on studies with mice, and the mice are not humans, of course, but we have a new very exciting direction to explore in our search for therapies with Alzheimer’s disease. “
CAA is already known to be a major cause of the brain dysfunction and bleeding weak, damaged cerebral arteries in some elderly patients, but no one has identified the way it is produced. It is also unclear the number of older adults suffer from CAA, because there is no way to make a clear diagnosis of the condition, unless sophisticated brain imaging studies are performed. But it is believed that this condition is widespread and CAA, either in association with independent of it or Alzheimer’s disease is a major cause of cognitive decline in the elderly.
The human brain normally produces amyloid β peptide-as part of neuronal function, but these peptides are deleted routinely from the brain, largely through blood vessels. However, most Alzheimer’s patients, the brain’s ability to clear amyloid-β is deteriorated and accordingly, a type of amyloid-β (Aß42) accumulates in amyloid plaques and other (Aß40) is accumulates in the arteries of the brain, resulting in CAA.
the research team found that CD36, a localized on the surface of immune cells and blood vessels, is a key protein accumulation in blood vessels Aß40. Protein is part of the innate immune system; its function is to act as a sensor to detect molecules that represent a danger to the host. Some of these molecules are derived from invaders, such as infectious agents organisms, but some are produced by the body, such as amyloid peptides, in excessive amounts, may become toxic.
“CD36 is a protein that binds treasure threatening molecules and activates a series of cellular responses designed to get rid of the threat,” says Dr. Iadecola. “Such responses include ramping inflammation and free radical production, both to neutralize criminals. However, in the case of amyloid-β, inflammation and free radicals damage the cerebral blood vessels and prevent separation efficient peptide through these vessels. This in turn sets off a vicious cycle that favors vascular accumulation of amyloid-β peptide and promotes the CAA. “
Dr . Iadecola and colleagues say may be possible to design new drugs that bind to CD36 at the precise site of the protein structure amyloid-β that adheres to, blocking the deleterious effects of receptor activation. “Now we know how it is produced, and so now we have a new goal,” he says.
This research was funded by grants from the National Institutes of Health, the American Heart Association and the Association Alzheimer.
Study co-authors include Dr. Laibaik Park, Joan Zhou, Dr. Ping Zhou, Dr. Sleiman El Jamal, Dr. Joseph Pierce, Andrea Arreguin, and Dr. Anrather Josef Weill Cornell Medical College; Pistick Rose and Dr. George A. Carlson McLaughlin Research Institute in Great Falls, Montana; Linda Younkin and Dr. Steven G. Younkin of the Mayo Clinic in Jacksonville, Florida; and Dr. Bruce McEwen S. Rockefeller University.
Weill Cornell Medical College
Weill Cornell Medical College, the medical school of Cornell University located in the city of New York, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in such places as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first time in the US to the degree of Doctor abroad. Weill Cornell is the birthplace of many medical advances – including the development of the Pap test to detect cervical cancer, the synthesis of penicillin, the first successful embryo biopsy pregnancy and birth in the US, the first clinical trial of gene therapy for Parkinson’s disease, and more recently, the first successful use of the world of deep brain stimulation to treat a patient with minimally conscious brain injury. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital / Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu .
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