Investigating the Role of Testosterone in Alzheimer's Disease

This project investigates the role of testosterone in beta amyloid production and assesses testosterone replacement therapy in animal and human studies as a potential therapy for theeffective treatment of Alzheimer's disease.

Several studies have reported that compared to controls, men with Alzheimer's disease (AD) and other dementias have lower serum testosterone levels:

• Professors Martins, Almeida and Gandy have shown that reducing blood levels of testosterone in men is associated with an increase in blood levels of beta amyloid.
• Supplementing neuronal cells in culture with testosterone has been shown to reduce beta amyloid levels and attenuate its toxicity.

Taken together, these studies suggest that the reduction in testosterone during aging could contribute to the development and the underlying causes of Alzheimer's disease.

Animal Study Findings

Preliminary findings from the animal studies indicate that testosterone replacement as a physiological dose reduces beta amyloid levels in both the blood and the cerebrospinal fluid. This work was presented at the Fifth International Society for the Study of Androgen Deficiency held in London in March 2007.

Further analysis of brain tissue from these animals is required to determine if testosterone can attenuate beta amyloid levels and oxidative stress in the brain.

Human Study Findings

The human study involves men with memory complaints, mild cognitive impairment (MCI) or Alzheimer's disease. It is divided into two parts:

1. a short term (pilot) study to determine the dose of testosterone to use - now completed
2. a long term, randomized study to assess the efficacy of testosterone at lowering beta amyloid and improving memory.

There have been 63 people screened for the long-term study of which 31 are eligible. Twelve have commenced the treatment.

In addition, an open labeled study has commenced in Perth with 25 men recruited to date. Preliminary work clearly demonstrates that testosterone treatment lowers beta amyloid levels in 4 months in most of the men in this study and lowers the hormone LH, a major contributor to Alzheimer's disease, in all participants.