APP and brain ischemia: We hypothesize that 1) coding variability together with significant differential gene expression in APP-Aß metabolism genes and LOAD GWAS loci may play a role in SVID and brain ischemia and 2) acute severe hypoperfusion-ischemia may prime APP misfolding, toxic soluble oligomers formation that may in the long term accumulate in the stable form of amyloid plaques, as described in elderly patients with vascular dementia22,23.