Alzheimer’s disease, the importance of Aβ and the hopes for chemo preventatives

A century after its discovery, Alzheimer's disease (AD) remains the most significant disease burden of ageing societies. Knowledge of the precise causes of AD is fundamental to rational preventative approaches and treatment. However, our current understanding is incomplete due to uncertainties in experimental models and the multifaceted nature of amyloid p, considered to be the causative agent associated with AD. These difficulties have not prevented experimental models, including rabbits, mice, worms, yeast and in vitro models, being used to explore AD preventatives and therapeutics. The difficulties have also led to a plethora of hypotheses on the cause of AD and a range of assays to measure outcomes in different treatments. For example, in the animal models some of the measured outcomes relate to cognition, plaque load or brain metals. Nevertheless, the most imp011ant outcome is what the chemo preventatives and treatments do for AD. Currently there is no cure for AD. Drugs such as the anticholine esterase inhibitors (e.g. Aricept, Namenda, Exelon, etc.) are usually prescribed for AD sufferers, but there is debate over their cost-effect iveness. The most exciting advance for prevention of AD has been simvastatin, a drug prescribed for hypercholesterolemia. Simvastatin is the second biggest selling drug after atorvastatin, another cholesterol-lowering drug which has little impact on AD. The advantage of simvastatin appears to be its lipophilic nature which allows it to cross the blood brain barrier. Other chemo preventatives in clinical trials target specific disease mechanisms and include metal chelators, antibodies, antioxidants, etc. This review will discuss the progress of AD drug research and outline various strategies and models used for testing them.