From the desk of

Bruce L. Miller, MD
Medical Director, JDFAF

Exciting New Advances in Alzheimer’s Disease Research

Remarkably, Alzheimer’s research has continued to advance in a year that has b een trou b led b y great financial insta b ility and The John Douglas French Alzheimer’s Foundation’s support for important research into the diagnosis and b asic mechanisms associated with Alzheimer’s disease remains steady and powerful. Funding for creative Assistant Professors at UCLA, UCSF and USC Keck School of Medicine is generating exciting new findings related to neuroimaging, gene expression, protein structure and drug discovery for Alzheimer’s disease and related disorders.  

Several types of new medications are currently b eing explored in clinical trials for Alzheimer’s disease. One major group of compounds appears to work b y diminishing the concentration of the extracellular b eta-amyloid protein within the b rain, while the other chief approach targets the intracellular protein tau. Some have suggested that the intensity of the arguments b etween the Beta-amyloid proponents (a b b reviated Bap, and given the acronym Baptists) and tau proponents (Taoists) has reached the intensity of religious wars. We all hope that b oth of these research groups will b e proven correct b ecause new therapies for Alzheimer’s disease are desperately needed.

Monoclonal anti b odies or vaccines that target the A-β42 protein work b y increasing the clearance of this protein from the b rain. Another way of diminishing this protein is to give compounds that diminish the production of A-β42 (so-called secretases). Both of these approaches are formally testing the “amyloid hypothesis” suggesting that Alzheimer’s disease is caused b y the a b normal accumulation of A-β42. Whether or not the toxicities of these medications will exceed their b enefits remains unknown, b ut b y the end of 2009 important new answers will emerge either supporting or refuting the idea that diminishing A-β42 is a via b le treatment for Alzheimer’s disease.

In parallel b ut distinctive efforts, sta b ilizing or eliminating the intracellular tau protein is b eing attempted. This idea is supported b y the finding that diminishing tau protects animals programmed to overproduce A-β42 from its toxic effects. The tau trials are just b eginning and no definitive answers are expected in 2009, b ut even if the A-β42 approaches fail, anti-tau compounds may still work. Finally, much to the surprise of many scientists, a compound called Dime b on, used for many decades in Russia, has shown promise in a large recently completed European trial. Dime b on is now moving into what is called a phase III trial in the United States which could lead to FDA approval for this medication within the next several years. Stay tuned!

Other noteworthy developments have emerged in Alzheimer’s disease related to diagnosis and drug screening. The discovery b y Shinya Yamanaka (jointly b ased in Kyoto, Japan and at UCSF’s Gladstone Institute) that human skin cells could b e transformed into stem cells and then converted into neurons has electrified the scientific community. Whether these skin cells can ever b e a via b le therapy remains in dou b t, b ut there is great excitement that these person-specific cells could b e used to screen for new medications, increasing the likelihood that our screening procedures for new compounds will translate more effectively into real treatments. In the area of diagnosis, new amyloid b inding imaging agents are b eing developed as a simple and powerful way to diagnose Alzheimer’s disease in the very earliest stages, in some instances even b efore the illness has manifested clinically. 

Your leadership and generosity is moving us all closer to the day when Alzheimer’s disease is a distant memory, and we all maintain the precious memories that are taken away with this terri b le illness. Our founder Dorothy Kirsten French reminded us to, “Forget not those who cannot remem b er.”

If you have questions about this research update or any research we are doing, please feel free to contact me through our website:     www.jdfaf.org

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