Invited Review for the Journal of Neurochemistry to coincide with the anniversary of Alois Alzheimer's famous presentation on the pathology of Auguste D. in November 1906.
Disease modifying therapy for AD?1
Article first published online: 2 OCT 2006
Journal of Neurochemistry
Volume 99, Issue 3, pages 689–707, November 2006
How to Cite
Golde, T. E. (2006), Disease modifying therapy for AD?. Journal of Neurochemistry, 99: 689–707. doi: 10.1111/j.1471-4159.2006.04211.x
- Issue published online: 2 OCT 2006
- Article first published online: 2 OCT 2006
- Received July 11, 2006; revised manuscript received July 27, 2006; accepted August 7, 2006.
Alzheimer's disease (AD) is the most common form of dementia in industrialized nations. If more effective therapies are not developed that either prevent AD or block progression of the disease in its very early stages, the economic and societal cost of caring for AD patients will be devastating. Only two types of drugs are currently approved for the treatment of AD: inhibitors of acetyl cholinesterase, which symptomatically enhance cognitive state to some degree but are not disease modifying; and the adamantane derivative, memantine. Memantine preferentially blocks excessive NMDA receptor activity without disrupting normal receptor activity and is thought to be a neuroprotective agent that blocks excitotoxicty. Memantine therefore may have a potentially disease modifying effect in multiple neurodegenerative conditions. An improved understanding of the pathogeneses of AD has now led to the identification of numerous therapeutic targets designed to alter amyloid β protein (Aβ) or tau accumulation. Therapies that alter Aβ and tau through these various targets are likely to have significant disease modifying effects. Many of these targets have been validated in proof of concept studies in preclinical animal models, and some potentially disease modifying therapies targeting Aβ or tau are being tested in the clinic. This review will highlight both the promise of and the obstacles to developing such disease modifying AD therapies.