CLEVELAND — It’s been known that women are disproportionately affected by Alzheimer’s disease. David Kang, PhD, said why that is was unknown, until now.
“Could be the first clue,” Kang said.
The Professor of Pathology at Case Western Reserve University explained the scientific community has long linked the brain protein tau as a hallmark signature of Alzheimer’s. Tau becomes toxic when too much accumulates in the brain. It builds up faster in women compared to men even before the onset of symptoms of the disease.
He believes the study he co-authored with his wife JungA ‘Alexa’ Woo, PhD, offers a significant reason why that is.
“What we found is that an enzyme called USP11 is expressed at naturally higher levels in females compared to males and this increase in USP11 causes an increase in tau pathology and greater susceptibility to Alzheimer’s disease,” Kang said.
This was something they stumbled upon. The initial goal of the study was to find enzymes that eliminate the chemical tag called ubiquitin used to remove excess tau from the brain.
After happening upon USP11, the study evolved to uncover a potential cause for women’s increased vulnerability to Alzheimer’s. They tested this idea on mice by removing the enzyme from both male and female brains.
“Eliminating USP11 protected females much more than males from tau pathology accumulation and cognitive decline,” Kang said.
Human and mouse brains, both cognitively normal and those affected by Alzheimer’s disease, were looked at for comparison as part of this study.
Researchers examined male and female brains and found the enzyme USP11 was expressed in higher levels in all the female brains, even those without Alzheimer’s.
Kang has been studying Alzheimer’s Disease for 25 years and this study began five years ago. A handful of graduate students and post-doctoral fellows are assisting with the research.
It was published this October.
“Now we have a culprit. We have a potential therapeutic target,” Kang said.
“Now we’re in a position where we can actually do something about that vulnerability.”
His lab’s goal now is to find current FDA approved drugs that could block USP11 and therefore potentially mitigate the risk of Alzheimer’s in women.
Kang wants to encourage pharmaceutical companies and other academic labs to explore this as well, hoping to develop a new medicine.
“It’s hope for all women,” he said.
