Cutting the Synaptic Cord

The earliest steps in Alzheimer's disease have proven tricky to target with therapeutics because they occur as part of normal brain activity and before symptom onset. This pathway now has been fleshed out by a trio of papers that have mapped a sequence of synaptic events leading to b-amyloid production and its sequelae, pointing to new therapeutic targets and drug delivery strategies (see Figure 1, "Mapping early Alzheimer's disease events and targets").

Two studies^1,2 address the endosomal processing events that occur within neuronal cells to convert amyloid precursor protein (APP) to b-amyloid (Ab), which is the major constituent of the amyloid plaques that are the hallmarks of AD.³...