Levetiracetam prevents Aβ production through SV2a-dependent modulation of App processing in Alzheimer's disease models.

In Alzheimer's disease (AD), amyloid-beta (Aβ) peptides are produced by proteolytic cleavage of the amyloid precursor protein (APP), which can occur during synaptic vesicle (SV) cycling at presynapses. Precisely how amyloidogenic APP processing may impair presynaptic proteostasis and how to therapeutically target this process remains poorly understood. Using knock-in mouse models of early Aβ pathology, we found proteins with hampered degradation accumulate at presynaptic sites.