Research: Sex hormone makes men less prone to Alzheimer’s

by RYO SASAKI
June 20, 2025

This schematic diagram explains that testosterone suppresses the mTOR signaling pathway via the cell membrane receptor GPRC6A, thereby enhancing autophagic activity and prompting decomposition of amyloid beta. (Provided by Akiko Mizokami)

FUKUOKA—Testosterone, a sex hormone produced primarily in male testes, could be the reason why men are less likely than women to develop Alzheimer’s disease, researchers with Kyushu University here said.

Alzheimer’s disease is believed to be caused by the accumulation of a protein called “amyloid beta” in the brain. The team’s experiments showed that administration of testosterone triggers a process that reduces that protein.

The researchers said their findings could help in the development of new therapies.

There are about twice as many female Alzheimer’s disease patients than male patients, studies in Japan and abroad have shown.

The research group said mechanisms behind the sex-based differences in patient numbers have not been determined, although some studies say a drastic decline in estrogen, a female sex hormone, in postmenopausal women is the primary factor.

The Kyushu University researchers decided to focus on testosterone to find out why men are less prone to the disease.

After the team removed testicles from male mice to reduce their testosterone levels, the accumulation of amyloid beta in them increased. However, the accumulation levels dropped in the mice when testosterone was administered.

An experiment using cultured cells showed that testosterone administration enhances the activity of microglia, which are immune cells in the brain.

Studies have shown that microglia have an “autophagy” function that decomposes abnormal proteins, including amyloid beta.

The university team’s study showed that testosterone plays a role in prompting decomposition of the substance responsible for Alzheimer’s disease and suppressing the onset of the illness, the scientists said.

“Establishing the cause of the sex-based differences in the onset of the disease is key to understanding the disease itself,” said Akiko Mizokami, a Kyushu University associate professor of dental science and neuroscience and a leading member of the research team. “We hope to continue with our study so we can help propose therapies and prophylactics.”

The research results were published in Advanced Science, a scientific journal https://doi.org/10.1002/advs.202413375).

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