Alzheimer’s Disease 2016: Discovery Of Gene Signature Traces Origin Of Disease

Researchers from the University of Cambridge have discovered a gene signature that can help understand the progression pattern of Alzheimer’s disease, making it possible for at-risk individuals to take preventive treatments that are under development well in time before the appearance of symptoms.

Alzheimer’s is a degenerative disease that causes acute problems with memory, thinking ability and behavior. It afflicts one in three senior citizens in the U.S., who have some form of dementia as a result of the disease. It is not possible to locate the abnormally formed brain proteins — amyloid beta and tau — that signal the onset of Alzheimer’s while a person is still alive. The inability to locate these abnormal proteins allows them to form plaques and tangles in the brain, which in turn kill neurons.

As of now, the disease remains incurable and its molecular origins are unknown.

ALZHEIMERS A woman, suffering from Alzheimer's desease, holds the hand of a relative in a retirement house in Angervilliers, eastern France, March 18, 2011. GETTY IMAGES/SEBASTIEN BOZON/AFP

However, in the new study published in the journal Science Advances, researchers were able to identify a specific signature of genes in parts of the brain that are most vulnerable to the disease. Their vulnerability stems from the weakness associated with the body’s defense mechanisms against the proteins in these regions.

“What we’ve tried to do is to predict disease progression starting from healthy brains,” Michele Vendruscolo, senior author and professor at the Centre for Misfolding Diseases at Cambridge’s department of chemistry, said in a press release. “If we can predict where and when neuronal damage will occur, then we will understand why certain brain tissues are vulnerable, and get a glimpse at the molecular origins of Alzheimer’s disease.”

According to the results, healthy young individuals with a different form of this gene signature could be more susceptible to Alzheimer’s later in life. It means that when preventative treatments for the disease are finally developed, these individuals stand to benefit the most.

For the study, researchers analyzed more than 500 samples of healthy brain tissues from the Allen Brain Atlas, identifying a signature of a group of genes in healthy brains. These were then compared with tissue from Alzheimer’s patients to show that the disease would progress in the same pattern in the all brains.

“Vulnerability to Alzheimer’s disease isn’t dictated by abnormal levels of the aggregation-prone proteins that form the characteristic deposits in disease, but rather by the weaker control of these proteins in the specific brain tissues that first succumb to the disease,” said Vendruscolo.

The results of the study have numerous benefits in the long run but in the short term, developing more effective animal models for the study of disease is possible. Till now, it was tough to breed genetically modified animals that could repeat the full pathology of Alzheimer's disease.

“It is exciting to consider that the molecular origins identified here for Alzheimer’s disease may predict vulnerability for other diseases associated with aberrant aggregation — such as ALS, Parkinson’s disease and frontotemporal dementia,” said Rosie Freer, a Ph.D. student in the department of chemistry at Cambridge and the study’s lead author.

“I hope that these results will help drug discovery efforts — that by illuminating the origins of disease vulnerability, there will be clearer targets for those working to cure Alzheimer’s disease,” she added.

Loading...
Join the Discussion