Posted 3 August 2006
Alzheimer Research Forum's 10th Anniversary Symposium: Mapping the Next Decade of Alzheimer Research
An ancillary event at the International Conference on Alzheimer's Disease 2006.
Ten years ago, the Alzheimer Research Forum was formally launched in Osaka, Japan, at the ICADRD. To mark this milestone, we held a symposium on "Mapping the Next Decade of Alzheimer Research." The symposium asked participants to consider key advances in Alzheimer disease research from the past decade and to look forward in a bold attempt to craft a research agenda for the next 10 years. Our speakers formed teams and prepared short presentations in which they attempted to synthesize major findings in several overlapping subject areas relevant to AD. In Madrid the discussion leaders led a group brainstorming session aimed at drafting a research roadmap for the next decade. We aimed to challenge the field to integrate findings and draw significant consensus toward building inclusive hypotheses that explain more fully the pathogenesis of this complex disease.
Discussion leaders included Konrad Beyreuther and Dennis Selkoe. Presenters included Bart de Strooper, David Holtzman, Takeshi Iwatsubo, Frank LaFerla, David Morgan, Li-Huei Tsai, Christine Van Broeckhoven, and Bruce Yankner.
Slide Presentations (Slides optimized for Internet Explorer)
Genetics of Alzheimer's disease
By Christine Van Broeckhoven
Comments and Discussion
AD Research Past and Future: View Slides by Takaomi Saido
Comment by Nikolaos Robakis— Submitted 4 May 2006
The paper by Doglio et al. has important implications for both the biological functions of the presenilin (PS) complex and the mechanisms by which PS FAD mutations promote neurodegeneration and other structural abnormalities in AD. The paper verifies previous results that presenilins regulate the PI3K/Akt cell survival pathway through a mechanism that is independent of the γ-secretase activity (Baki et al., 2004). This report is also consistent with recent evidence that FAD mutations may promote cell death and AD-related tau hyperphosphorylation through a mechanism that involves loss of presenilin function in the PI3K/Akt/GSK-3 and other cell signaling pathways (Baki et al., 2004; Kang et al., 2005). This last concept is in contrast to the widely held view that FAD mutations cause a gain of presenilin γ-secretase function, thus increasing production of neurotoxic species like Aβ1-42 (see, however, Alzforum debate on Gain or Loss of Function—Time to Shake up Assumptions on γ-Secretase in Alzheimer disease?). The data on aph-1/aPKC/PAR-1 indicate a new pathway that may also contribute to tau phosphorylation. Clearly, new exciting data emerging in the last 2 years from several laboratories promote novel concepts not only for the biological functions of PS1 but also for the mechanisms by which presenilin FAD mutations induce the specific neuropathology associated with AD.