All components of the AβDP degradation reaction (hitherto only demonstrated in solution in vitro): the main substrate (Aβx-40), the enzyme (BACE2), and its putative degradation product (Aβx-34), we found highly colocalised in discrete intracellular vesicles in human brain neurons, (and not astrocytes), suggesting that at least some of the AβDP activity generating Aβx-34 takes place intra-neuronally and physiologically during lifetime, before the onset of AD pathology, in both normal and DS brains. Here, BACE2 is linked to Dravet syndrome.