Testosterone's Role in Reducing Alzheimer's Disease Risk in Men

The schematic representation provided by Akiko Mizokami illustrates how testosterone suppresses the mTOR signaling pathway via the receptor GPRC6A on the cell membrane, subsequently increasing autophagic processes to break down amyloid beta. Researchers from Kyushu University in Fukuoka propose that this hormone, which is primarily produced in the testes, may be the reason that men exhibit a lower prevalence of Alzheimer's disease compared to women.

Alzheimer's disease is attributed to the buildup of amyloid beta protein in the brain, and the researchers found that administering testosterone effectively reduces this accumulation. Notably, studies indicate that female patients outnumber male patients with Alzheimer's disease by a factor of two, but the underlying reasons for this disparity remain largely unexplored. Some research suggests that the sharp decline in estrogen levels following menopause could be a significant contributing factor.

To investigate the protective role of testosterone, the research team conducted experiments where they castrated male mice to diminish their testosterone levels. They observed that this led to an increase in amyloid beta accumulation. Conversely, when testosterone was reintroduced, the levels of amyloid beta decreased. The researchers also conducted cell culture experiments, which revealed that testosterone enhances the activity of microglia—immune cells in the brain that play a critical role in autophagy and the breakdown of abnormal proteins like amyloid beta.

The findings indicate that testosterone is integral to the decomposition of the protein linked to Alzheimer's disease and may help delay its onset. Akiko Mizokami emphasized the importance of understanding the sex-based differences in disease onset to develop effective treatments and preventive measures. The results of this investigation have been published in the journal Advanced Science.