12th International Conference on Alzheimer's Disease (ICAD), Vienna, Austria (2009)

21 July 2009. In like a lamb, out like a lion. It’s a full season too late for this variation on the March weather proverb, but hopefully our generous readers will forgive their roving reporter for bending it anyway, because starting meekly and finishing with a roar is exactly what the Alzheimer’s Association’s 12th International Conference on Alzheimer’s Disease (ICAD) did when it unfolded in Vienna 11-16 July. And it is not about changing weather, either. All week, the Austrian capital bathed meeting attendees in sparkling sunshine (which seemed to seduce many into sneaking off for daytrips into this beautiful city as attendance seemed a bit sparse at times, but no names shall be named). No, the scientific program started with humbling reports of the failure – abject and otherwise – of the latest round of clinical trials. The program continued with confirmatory studies on the ability of exercise, a heart-healthy diet, and modest drinking while one is cognitively healthy, to modify one’s risk of cognitive decline somewhat. This is an important life message people should take to heart, but it is not the kind of news close followers of the field are looking for. But then the last morning – when many had departed, the exhibit hall was emptied out, and the press room had closed up shop – featured within the space of three hours arguably the biggest news in Alzheimer’s disease (AD) genetics research in the past decade. Three independent genomewide association studies, one being the largest performed to date on some 4,000 cases, together reported three new genes for late-onset AD. Hence, overall comments about ICAD in Vienna went from a plaintive “I haven’t heard anything really new” at the beginning to a confident “We can declare three new genes for Alzheimer’s” at the end. Most remarkable from an observer’s perspective was the consensus among independent genetics groups that the new genes would likely hold up to scrutiny in future studies even if their individual effect was small. When is the last time you remember applause and nodding faces, not skepticism or criticism, greeting the first introduction of a new candidate gene at a major AD conference? The genes reported today are ApoJ (aka clusterin), CR1 (which encodes a complement receptor), and PICALM (which encodes an endocytic gene). Together, they point partly to amyloid-β (Aβ) generation/clearance playing a role in late-onset AD, said Philippe Amouyel of the Institute Pasteur in Lille, France, but more broadly, they also implicate other upstream processes as leading to AD pathology and symptoms. “The GWAS data suggest that innate immunity and cholesterol are key themes in the disease,” said Julie Williams of Cardiff University, UK. Regarding clinical trials, the news in Vienna was mostly dire. Among the trials that reported results, GSK’s Phase 3 rosiglitazone program failed, the ADCS’s valproate and DHA trials were negative, as were the Phase 2b trials of AstraZeneca’s α4β2 nicotinic acetylcholine receptor agonist AZD3480 and of a monthly implant formulation of donepezil called mimopezil. The large anti-amyloid trials are many months to years away from yielding results, and without substantiation the rumors that inevitably fly in such periods of suspended animation are not worth reporting. The presentation by Bengt Winblad of the Karolinska Institute in Stockholm, Sweden, of Novartis’s CAD106 ac-