PICALM and Alzheimer disease: Two recent extensive genome-wide association studies (GWAS), comprising 12,000 probable AD cases and 18,000 age-matched non-demented controls [22,23], revealed three new candidates for genetic risk of developing late onset or sporadic AD: CLU, CR1 and PICALM. Phosphatidylinositol-binding clathrin assembly protein (PICALM) is involved in synaptic neurotransmitter release and intracellular trafficking [24-26], whilst complement component (3b/4b) receptor 1 (CR1), the main receptor of complement C3b protein, binds Aβ and thus may promote clearance [27-30].