Mouse Study Points to Why Alzheimer’s Affects Women More Than Men

MONDAY, Oct. 10, 2022 (HealthDay News) – Women are diagnosed with Alzheimer's disease twice as often as men. Now researchers think they know why.

A new study found evidence in mice and human brain tissue that may explain the differences, according to researchers from Case Western University in Cleveland.

Female brains showed a higher expression of an X-linked enzyme than male brains. The enzyme is called ubiquitin-specific peptidase 11 (USP11). This resulted in greater accumulation of a protein called tau that is linked to Alzheimer's disease.

“This study sets a framework for identifying other X-linked factors that could confer increased susceptibility to tauopathy in women,” said study co-author David Kang. The findings were published Oct. 4 in the journal Cell.

“In terms of implications, the good news is that USP11 is an enzyme, and enzymes can traditionally be inhibited pharmacologically,” Kang said in a journal news release. “Our hope is to develop a medicine that works in this way, in order to protect women from the higher risk of developing Alzheimer’s disease.”

One potential explanation for why women have more Alzheimer’s disease has been that women exhibit significantly higher tau deposits in the brain.

Eliminating excess tau begins with the addition of a chemical tag called ubiquitin to the tau protein, according to the study. A dysfunction of this process can lead to abnormal accumulation of tau.

Researchers looked for increased activity of the enzymatic systems that either added or removed the ubiquitin tag.

That led to the finding that female mice and humans both naturally expressed higher levels of USP11 than men. They also found that USP11 levels correlate strongly with brain tau pathology in females, but not in males.

When researchers genetically eliminated USP11 in a mouse model, the females were protected from tau pathology and thinking impairment. Males were also protected against tau pathology in the brain, but not as much as females.

While this suggests that excessive activity of the USP11 enzyme in females drives those increases in tau pathology, mouse models may not fully show what will happen in humans.

More information

Alzheimers.gov has more on Alzheimer’s disease.

SOURCE: Cell, news release, Oct. 4, 2022