Disease Modifying Therapeutic Strategies in Alzheimer's Disease Targeting the Amyloid Cascade

Alzheimer's Disease (AD) is a progressive and devastating neurodegenerative disorder affecting the brain. It is the most common form of late-life dementia and is one of the leading causes of death in the developed world. Due to the ageing population and improvement in diagnosis it is expected that the number of diagnosed AD patients will increase from the current level of ∼5 million to ∼22 million by 2025. Acetylcholine-based therapies, currently the only treatment regimes approved for AD, will also be the basis for treatment in the near future. However, progression of the disease is not affected by acetylcholinesterase inhibitors; rather it is a symptomatic treatment which can delay deterioration of cognitive symptoms for up to six months. Pharmaceutical companies are now investing their efforts in the development of diseasemodifying treatments for AD. The rationale for new drug design is based on the amyloid cascade hypothesis, which proposes that accumulation of amyloid beta peptide is the key event that triggers the pathological events in AD. The most promising, emerging approaches for the treatment of AD, targeting the release, the aggregation and the clearance of Abeta will be discussed.