PARIS, Oct. 5 (Benin News) –
Tests in mice and human brain tissue reveal a mechanism that may explain gender differences in Alzheimer’s disease, including why women are more vulnerable.
As researchers published in the journal ‘Cell’, women’s brains show higher expression of an X-linked enzyme called peptidase 11 (USP11) than men’s, leading to greater accumulation of a protein called tau.
“This study establishes a framework for identifying other X-linked factors that may confer increased susceptibility to tauopathy in women,” says study co-author David Kang of Case Western Reserve University ( United States).
Women suffer from Alzheimer’s disease twice as often as men. The mechanistic basis for this increased vulnerability is unclear, but one possible explanation is that women have significantly more tau deposits in their brains.
The process of removing excess tau begins with adding a chemical tag called ubiquitin to tau. Since a malfunction in this process can lead to abnormal accumulation of tau, Kang and Jung-A Woo, co-author of the study at Case Western Reserve University, looked for increased activity of enzyme systems that add or remove the ubiquitin tag.
They found that female mice and humans naturally express higher levels of USP11 in the brain than males, and that USP11 levels are strongly correlated with tau pathology in the brains of females, but not males. .
Furthermore, when they genetically deleted USP11 in a mouse model with brain tau pathology, females were preferentially protected from tau pathology and cognitive impairment. Men were also protected against tau pathology in the brain, but not to the same extent as women.
The results suggest that excessive USP11 enzymatic activity in women underlies their increased susceptibility to tau pathology in Alzheimer’s disease. However, the authors caution that mouse models of tauopathy may not fully reflect the sexual dimorphism of tau pathology seen in humans.
“In terms of implications, the good news is that USP11 is an enzyme, and enzymes can traditionally be pharmacologically inhibited,” says Kang. Our hope is to develop a drug that works in this way, to protect women against the increased risk of developing Alzheimer’s disease.