07 Dec 2001

The Center for Neurodegenerative Disease Research (CNDR) at the University of Pennsylvania School of Medicine organized the 2nd Annual CNDR Retreat as a one day symposium entitled "Emerging Alzheimer's Disease Therapies: Focusing on the Future," which was held on November 7, 2001, at the University of Pennsylvania in Philadelphia, Pennsylvania. John Q. Trojanowski and Virginia M.-Y. Lee, codirectors of CNDR, formulated a scientific agenda that considered a number of novel therapeutic approaches for the treatment of Alzheimer's disease (AD). Briefly, the approaches are those that target prevention or elimination of brain amyloid deposits resulting from accumulations of Aβ fibrils. Although fibrillar Aβ deposits in the extracellular space, known as senile plaques (SPs), and intraneuronal aggregates of tau fibrils, known as neurofibrillary tangles (NFTs), are the hallmark amyloid lesions of the AD brain, most patients with familial or sporadic forms of AD also exhibit a third type of amyloid lesion, known as a Lewy body, which is formed by intraneuronal accumulations of α-synuclein fibrils (1-3). Thus, AD is a brain amlyloidosis wherein at least three different building block proteins or peptides undergo pathological fibrillization to form deposits of amyloid within and outside neurons. Nonetheless, because most progress in the last decade of AD research has been made towards identifying therapeutic targets to prevent or eliminate amyloid deposits formed by Aβ fibrils, the symposium concentrated on emerging therapies for AD that are directed at these targets. This brief report summarizes highlights from the presentations at this symposium and it is notable that the presentations reflect the remarkable progress in understanding AD in the last decade since all of the potential therapeutic interventions described at the symposium resulted from insights into basic mechanisms of AD that have emerged only within the past 10 years, and they remain to be tested for their therapeutic efficacy (4-5). After Trojanowski opened the symposium by providing a brief overview of the major strategies for preventing or eliminating Aβ deposits upon which each presentation was based, the following 25-minute talks were given by 11 different speakers from industry and academia.—John Trojanowski