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Why Down syndrome leads to Alzheimer's disease

Fri, Oct 24, 2014, 12:12 PM
New York, Oct 24 : By the age of 40, nearly 100 percent of all individuals with Down syndrome develop changes in the brain associated with Alzheimer`s disease and researchers have now established the link behind the two disorders.

Down syndrome is characterized by an extra copy of chromosome 21, the most common chromosome abnormality in humans, and significantly lower levels of protein called sorting nexin 27 (SNX27).

"Our study reveals how SNX27 regulates the generation of beta-amyloid - the main component of the detrimental amyloid plaques found in the brains of people with Down syndrome and Alzheimer's," said author Huaxi Hu, a professor at Sanford-Burnham Medical Research Institute in the US.

"The findings are important because they explain how beta-amyloid levels are managed in these individuals," Hu said.

Beta-amyloid is a sticky protein that is toxic for neurons.

The combination of beta-amyloid and dead neurons form clumps in the brain called plaques. Brain plaques are a pathological hallmark of Alzheimer's disease and are implicated in the cause of the symptoms of dementia.

"We found that SNX27 reduces beta-amyloid generation through interactions with gamma-secretase - an enzyme that cleaves the beta-amyloid precursor protein to produce beta-amyloid," Xin Wang, a postdoctoral fellow in Xu's lab and first author of the study pointed out.

"When SNX27 interacts with gamma-secretase, the enzyme becomes disabled and cannot produce beta-amyloid," Wang noted.

"Lower levels of SNX27 lead to increased levels of functional gamma-secretase that in turn lead to increased levels of beta-amyloid," he pointed out.

The researchers went on to reveal how lower levels of SNX27 in Down syndrome are the result of an extra copy of an RNA molecule encoded by chromosome 21 called miRNA-155.

The study was published in the journal Cell Reports.
Agency: IANS
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