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

ABSTRACT: 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 the major components of amyloidogenic machinery namely, APP and secretases are discretely organized into nanodomains of high local concentration compared to their immediate environment in functional zones of the synapse. Additionally, with the aid of multiple models of Alzheimer's disease (AD), we confirm that this discrete nanoscale chemical map of amyloidogenic machinery is altered at excitatory synapses. Furthermore, we provide realistic models of amyloidogenic processing in unitary vesicles originating from the endocytic zone of excitatory synapses. Thus, we s

SUBMITTER: Kedia S 

PROVIDER: S-EPMC7773964 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature