Cell: Why women are more likely to develop Alzheimer's

Researchers at Case Western Reserve University have discovered a mechanism in brain tissue that could explain why women are more likely to develop Alzheimer's

Specifically, the researchers found that women expressed higher amounts of an enzyme in their brains than men, resulting in greater accumulation of a protein called tau

This enzyme is called ubiquitin-specific peptidase 11 (USP11) and is X-linked, meaning it is present in genes on the X chromosome, one

"We are particularly excited about this finding because it provides a basis for the development of new neuroprotective drugs," said David Kang, Professor of Pathology at Case Western Reserve Medical School, "This study also provides a framework for identifying other x-related factors that may increase susceptibility

Alzheimer's disease, women and tau protein

Women develop Alzheimer's disease about twice as often as

"When a particular tau protein is no longer needed for the function of its nerve cells, it is often designated for destruction and elimination," Kang said

The process of clearing excess tau proteins begins with the addition of a chemical tag

Because dysfunction of this equilibrium process can lead to abnormal accumulation of tau protein in Alzheimer's patients, Kang and Jung-A Woo, an assistant professor at Case Western Reserve University, conducted a high-level study into why this

Specifically, they looked for an increase in the activity of the enzyme system that controls ubiquitin tag removal, as overactivation on this side of the balance can lead to pathological tau protein accumulation

Professor Kang said: "We think that if this can be identified, then it can provide a basis for the development of new drugs that restore the proper balance

They found that levels of USP11 expressed naturally in women's brains were higher than in men, and that USP11 levels were strongly associated with brain tau protein pathology in women, but not

Possible protection for women

The researchers also found that when they genetically eliminated USP11 from a mouse model of brain tau protein pathology, female mice were preferentially protected from tau protein pathology and cognitive impairment

These results suggest that overactivity of the USP11 enzyme in women's bodies leads to increased

"In terms of effects, the good news is that USP11 is an enzyme that has traditionally been pharmacologically inhibited