Scientists unclear on how brain change can lead to Alzheimer's

Washington: A new study suggests that the Alzheimer's drug candidates CMS121 and J147 may be useful for treating a broader array of conditions and points out a new pathway that links normal ageing to Alzheimer's disease.

According to Pamela Maher, a senior staff scientist at Salk and a co-corresponding author of the new paper, "This study further validated these two compounds CMS121 and J147, not only as Alzheimer's drug candidates but also as potentially more widely useful for their anti-ageing effects,"

Old age is the biggest risk factor for Alzheimer's disease -- above the age of 65, a person's risk of developing the disease doubles about every five years. However, at a molecular level, scientists aren't sure what occurs in the brain with ageing that contributes to Alzheimer's.

"The contribution of old age-associated detrimental processes to the disease has been largely neglected in Alzheimer's disease drug discovery," says Antonio Currais, a Salk staff scientist and first author of the new paper.

Maher and David Schubert, the head of Salk's Cellular Neurobiology Lab, previously developed CMS121 and J147, variants of plant compounds with medicinal properties. Both compounds tested positive for their ability to keep neurons alive when exposed to cellular forms of stress related to ageing and Alzheimer's disease. Since then, the researchers have used the drug candidates to treat Alzheimer's in animal models of the disease.

But experiments revealing exactly how the compounds work suggested that they were targeting molecular pathways also known to be important in longevity and ageing. "The bottom line was that these two compounds prevent molecular changes that are associated with ageing," says Maher.

"There was already some data from human studies that the function of mitochondria is negatively impacted in ageing and that it's worse in the context of Alzheimer's," says Maher. "This helps solidify that link."