Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease

Despite intuitive insights into differential proteolysis of amyloid precursor protein (APP), the stochasticity behind local product formation through amyloidogenic pathway at individual synapses remain unclear. Here, we show that major components machinery namely, APP and secretases are discretely organized nanodomains high concentration compared to their immediate environment in functional zones synapse. Additionally, with aid multiple models Alzheimer's disease (AD), confirm this discrete nanoscale chemical map is altered excitatory synapses. Furthermore, provide realistic processing unitary vesicles originating from endocytic zone Thus, how an alteration synaptic organization contributes dynamic range C-terminal fragments β (CTFβ) production, defining heterogeneity synapses, leading long-term deficits as seen AD.