Androgen Loss May Lead To Alzheimer’s

The team’s findings – appearing as a letter to the editor in the Sept. 22 issue of the Journal of American Medical Association – bolster sparse research on the adverse effects of age-related testosterone depletion in the brain and may lead to future development of hormone replacement therapies.

“Our findings strongly suggest that normal age-related testosterone depletion is one of the important changes that promote Alzheimer’s disease in men,” said Christian Pike, senior author of the study and an assistant professor at the USC Leonard Davis School of Gerontology.

“Understanding how these changes increase vulnerability to the disease is critical not only for elucidating Alzheimer’s development, but also for identifying those persons most at risk,” Pike said.

While the link between estrogen loss in women and increased susceptibility to a variety of diseases – including Alzheimer’s – has long been well established, there has been less focus on the health effects of hormonal depletion in men.

Only within the last few years has the range of impairments – including osteoporosis and the loss of muscle mass, strength and function known as sarcopenia – linked to decreased testosterone levels become a recognized clinical syndrome called ADAM, or androgen deficiency in aging males. Androgens are male sex hormones.

The data collected by the USC team – Pike, Lilly Chang and Frank Stanczyk of the Keck School of Medicine of USC, and Emily Rosario of the USC Andrus Gerontology Center – suggests that the brain is another tissue that experiences age-related testosterone loss and that increased vulnerability to Alzheimer’s disease should now be considered a component of ADAM.

Using brain tissue from 45 (previously consenting) deceased male subjects and an established medical scale of neuropathology, the researchers divided their samples into three categories: those considered neuropathologically normal with no clinical history of cognitive impairment (these were the controls); those who exhibited mild neuropathological changes; and those who had Alzheimer’s disease.

“We found that brain levels of testosterone are significantly lower in [Alzheimer’s] subjects compared with the control subjects,” the researchers wrote. “We found that brain levels of testosterone are also significantly reduced in men with mild neuropathology consistent with early Alzheimer’s disease.”

Furthermore, the team demonstrated that estrogen levels in the subjects’ brains were affected by neither advancing age nor the presence of Alzheimer’s disease.

“Thus far, our research tell us that testosterone has at least two critical brain functions relevant to Alzheimer’s disease,” Pike said. “It protects neurons from injury, and it reduces levels of beta-amyloid, the protein widely implicated as a causal factor in the disease.”

“We believe that the loss of testosterone with advancing age creates a more hostile neural environment that promotes accumulation of toxic beta-amyloid protein while leaving neurons less able to survive the insult,” he added.

Alzheimer’s disease, first described in 1906 by German physician Alois Alzheimer, involves the degeneration of nerve cells in the cerebral cortex and hippocampus, restricted parts of the brain associated with memory.

The national Alzheimer’s Association estimates that the disease currently affects approximately 4 million Americans, half of which are men. By the year 2050, it is predicted that an additional 10 million could suffer from the illness.

And much more research remains before a cure can be found.

Pike and his colleagues seek to determine the mechanism by which testosterone depletion places the brain at increased risk for the mentally debilitating disease.

“Advancing age is the most significant risk factor for Alzheimer’s disease,” Pike said. “We now have to find the age-related changes that combine to promote the disease.”