Whilst analysis of end-stage post-mortem AD brain reveals that oligomeric Aβ accumulates at the synapse55–57, and synthetic Aβ can induce loss of synaptophysin mRNA in free-floating human brain slices58,59, direct evidence that the Aβ present in AD brains is synaptotoxic to human brain tissue is lacking. This evidence concerns the gene SYP and Alzheimer disease.