People with Down's syndrome, who inherit an extra copy of chromosome 21, usually develop Alzheimer's disease by middle age; by their 30s or 40s, their brains often display the alterations and protein deposits characteristic of Alzheimer's disease.
Interestingly, the gene for one of the proteins, APP, which deposits in the characteristic plaques of Alzheimer's disease, is on chromosome 21, and mutations in this gene are associated with early-onset Alzheimer's Disease.
Alzheimer's disease appears to involve misprocessing of APP, which leads to protein deposits characteristic of the disease. Now, a research team led by Jorge Busciglio and Bruce Yankner has found that the reason Down's syndrome patients develop these deposits may reside in their mitochondria. Mitochondria are microscopic structures which function as “powerhouses," providing our cells with usable energy.
The results are reported in today's issue of Neuron.
Busciglio, Yankner and colleagues noticed that if they prevented the correct function of mitochondria in normal human brain cells, the cells would begin to display the alterations characteristic of Alzheimer's disease. The researchers reasoned that Alzheimer's disease in Down's syndrome patients may result from abnormal mitochondrial function.
Busciglio, Yankner, and colleagues then examined the mitochondria of Down's syndrome patients' brain cells and found that they were indeed impaired. Therefore, having either an extra copy of APP, or a mutation within APP, leads to impaired mitochondrial function.
The impaired function of these mitochondria appears to lead to further misprocessing of APP, which in turn results in protein deposits which render cells more vulnerable, eventually leading to the tragic cognitive decline associated with Alzheimer's disease.
“In the light of these findings, future therapies for Alzheimer's disease or Down's syndrome should seek to restore the normal function of mitochondria”, said Busciglio. It may be that restoring the normal function of mitochondria will protect neurons and ameliorate the cognitive decline of Alzheimer's disease.
[Contact: Bruce Yankner, Jorge Busciglio]