Synaptic phosphoproteome modifications and cortical circuit dysfunction are linked to the early-stage progression of alpha-synuclein pathology

Lewy body inclusions enriched with aggregated forms of the presynaptic protein alpha-synuclein (aSyn) are a hallmark of synucleinopathy diseases such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). To model this pathology, C57 mice were injected in the cortex or striatum with preformed fibrils (PFFs) prepared from mouse aSyn to induce the aggregation of the endogenous mouse protein. Monomeric aSyn was injected as a control. Aggregated aSyn was detected via immunohistochemical staining in the sensorimotor cortex at 1- and 3-months post-injection in PFF-injected mice, but not monomer-injected animals. Phosphoproteomics analysis was carried out on homogenates from the sensorimotor cortex of mice inoculated with PFFs or monomer, 3 months post-injection, and the data are presented here.