Expression of p24α2 in mammalian brain (651.4)

Dysregulated metabolism and accumulation of amyloid‐β (Aβ) peptides in brain underlies the pathogenesis of Alzheimer's disease. Aβ is predominantly generated in neuronal cells and is considered to be secreted from the presynaptic terminals in a synaptic activity‐dependent manner. The p24 family member p24α2 has been reported to attenuate Aβ generation through inhibiting γ‐secretase processing of amyloid precursor protein (APP). However, the expression and localization of p24α2 in brain has not been examined. Here, we performed immunohistochemical staining and subcellular fractionation for p24α2 using mouse brain. Immunostaining showed that p24α2 is broadly distributed in the grey matter of the central nervous system and is predominantly localized at the synapses. Subcellular fractionation indicated that p24α2 is condensed at the active zone‐docked synaptic vesicles in the presynaptic terminals. During development, p24α2 is expressed in postnatal period at the highest level and gradually declines. We also confirmed that APP and γ‐secretase components are localized at the active zone‐docked synaptic vesicles. Our results suggest a novel functional implication of p24α2 in regulation of synaptic transmission and synaptogenesis and provides supportive evidence for a role of p24α2 in regulation of Aβ generation and secretion in brain.