By age 40, almost 100% of individuals with Down syndrome develop the brain modifications that lead to Alzheimer’s disease. Now, a new research claims to have unveiled the mechanism that puts individuals with Down syndrome at such high threat of Alzheimer’s.
Down syndrome is triggered by the most common chromosome problem in humans – an additional copy of chromosome 21. around 1 in 700 babies in the US are born with Down syndrome.
Along with a mild to moderate intellectual incapability, a characterizing undesirable effect of Down syndrome is the enhanced risk of Alzheimer’s disease. By age 40, almost 100% of individuals with Down syndrome will have modifications in their brain that result inAlzheimer’s; 1/4 show symptoms of Alzheimer’s-type dementia by the age of 35 and 3/4 by the age of 65.
As individuals with Down syndrome are now living more time than ever before – average life span is 60 today, but was just 25 in 1983 – study is addressing how the quality of life of individuals with Down syndrome may be enhanced.
The scientists, from the Sanford-Burnham Medical Research Institute, identified that both mice bred to share characteristics with Down syndrome and people with Down syndrome have considerably reduced levels of a protein called sorting nexin 27 (SNX27)
SNX27 performs a role in keeping receptors on the surface of brain cells. As these receptors are essential for neurons to fire effectively, reduced levels of SNX27 damage neuron activity, which results in cognitive issues.
Also, SNX27 – the team identified – regulates beta-amyloid production. Beta-amyloid is the “sticky protein” toxic to neurons, which – combined with dead neurons – clumps up in plaques inside the brain. These plaques are regarded to be the characteristic of Alzheimer’s.
“We identified that SNX27 decreases beta-amyloid generation via interactions with gamma-secretase – an enzyme that cleaves the beta-amyloid precursor protein to generate beta-amyloid,” says Xin Wang, PhD, initial author of the publication.
“When SNX27 communicates with gamma-secretase, the enzyme turns into disabled and can’t produce beta-amyloid. Reduced levels of SNX27 result in enhanced levels of functional gamma-secretase that in turn result in enhanced levels of beta-amyloid.”
The scientists identified that these reduced levels of SNX27 in individuals and mice with Down syndrome are triggered by an extra copy of miRNA-155 – an RNA molecule encoded by chromosome 21 that impacts SNX27 production.
Determining the ‘complex mechanism’ driving Alzheimer’s-Down connection
Mapping the procedure that results in this outcome, the scientists identified that the additional copy of chromosome 21 implicit in Down syndrome leads to raised levels of miRNA-155, which result in reduced levels of SNX27.
The part of this cascade that results inAlzheimer’s is that the decreased levels of SNX27 result in a raise of active gamma-secretase, which increases production of beta-amyloid and, therefore, the plaques in the brain that lead to Alzheimer’s.
“We have described a rather complex mechanism that describes how SNX27 levels indirectly cause beta-amyloid,” states author Huaxi Hu. adding:
“While there may be a lot of aspects that play a role to Alzheimer’s characteristics in Down syndrome, our research facilitates an method of suppressing gamma-secretase as a means to avoid the amyloid plaques in the brain identified in Down syndrome and Alzheimer’s. The results are essential because they describe how beta-amyloid levels are managed in these people.”