The genetic mechanism which destroys brain cells is responsible for early development of Alzheimer's in people with Down syndrome, say researchers.
Researchers at the University of British Columbia and Vancouver Coastal Health Research Institute have discovered that the genetic mechanism which destroys brain cells is responsible for early development of Alzheimer’s Disease in people with Down syndrome and for development of Alzheimer’s Disease in general population.
The research, which is published in the Journal of Biological Chemistry, provides a potential new target for drugs that could potentially prevent dementia in people with either condition.
In the study, lead author Weihong Song, MD, PhD, of the UBC Faculty of Medicine, and colleagues found that excessive production of the protein, Regulator of Calcineurin 1 (RCAN1) sets in motion a chain reaction that kills neurons in the hippocampus and cortex in people with Down syndrome and Alzheimer’s.
“Neuronal death is the primary reason for the memory loss and other cognitive impairments of Alzheimer’s Disease, and it’s the main reason people with Down Syndrome develop Alzheimer’s Disease long before most people, usually in their 30s,” said Song in a press release. “By looking for the common elements of both conditions, we were able to pinpoint how and why the deterioration occurs.”
Alzheimer’s disease (AD) is the most common form of dementia, which usually affects people over age 60. The Alzheimer Society of Canada estimates that the disease affects more than 238,000 Canadians, and that by 2031 about 750,000 Canadians will suffer from AD and related dementias.
Down syndrome (DS) is a congenital anomaly that includes developmental delays and learning disabilities. A 2002 report by the Public Health Agency of Canada stated that about one in 800 Canadian newborns have the condition; the average lifespan for those with Down syndrome is 49 years. People with DS have an extra copy of the gene that produces RCAN1, which leads to its excess production. The resulting neuronal death—with symptoms that mirror those of AD patients—is one of the prime reasons for the shortened lifespan of people with DS.
The research team discovered that some AD patients have similarly elevated levels of the RCAN1 protein, despite having two copies of the responsible gene. It’s still unknown why, though Dr. Song speculates that the gene’s overexpression might be triggered by stroke, hypertension or the presence of a neurotoxic protein, called beta amyloid, that typically collects into clumps in the brains of people with AD — what he describes as a “vicious cycle” in which one destructive factor exacerbates another.
But now that the culprit gene and protein have been identified, “we can develop therapies that interfere with the gene’s ability to produce that protein, and hopefully short-circuit the destruction of brain cells,” said Song.
To read the Journal of Biological Chemistry study, click here.