BACE1 and Alzheimer disease: An elevated Aβ34/Aβ42 ratio in the prodromal stage of AD could indicate that, at early stages of Aβ plaque formation (i.e., decreased CSF-Aβ42 levels41), the increased levels and amyloidolytic activity of BACE1 elicit a defense reaction (i.e., increased generation of Aβ34 to facilitate amyloid clearance).