The two most common neurodegenerative diseases--Alzheimer's and Parkinson's--are accelerated by the same genes, according to a new study. The genes appear to play a role in inflammation, suggesting that soothing errant immune cells might slow down the progression of these diseases.
Other lines of evidence have pointed to a conspiracy between Alzheimer's disease (AD) and Parkinson's disease (PD). People with one disease are at heightened risk of developing the other, for example. In addition, particular types of protein tangles are hallmarks of both diseases, and both spark inflammation in the brain.
Several genes have been linked to increased risk of PD or AD, but a team from Duke University in Durham, North Carolina, looked for a different type of gene: one that helps determine how quickly disease takes hold. Both diseases start fairly subtly, and they aren't obvious until many neurons have died. Thus, genes that speed up either disease's progression would lead to diagnosable symptoms at a younger age. Last year they linked a stretch of chromosome 10 to the age at which someone diagnosed with AD or PD had come down with symptoms, otherwise known as the age of onset. (The stretch was no use, however, for predicting whether a healthy person was likely to contract one of these diseases.)
Now the team, led by Margaret Pericak-Vance and Yi-Ju Li, has found the genes on chromosome 10 responsible for a relatively early or late onset. The researchers tested autopsied brain slices from AD patients and controls to see which chromosome 10 genes were differentially active; they identified four genes. They then scanned the genomes of 1773 AD patients and 635 PD patients to see whether variations in these genes correlated with age of onset. Two very similar, neighboring ones, GSTO1 and GSTO2, fit the bill, they report in the 15 December issue of Human Molecular Genetics.
The products of these genes appear to contribute to inflammation, among other things. The discovery suggests that "inflammation plays a crucial role in the progression of both," says neurobiologist Mike Hutton of the Mayo Clinic in Jacksonville, Florida. If it holds up--and Hutton and others emphasize that the study should be replicated--"it's opened up a new area" of research, on how GSTO1 and GSTO2 and their ilk can be harnessed to slow these diseases.