Fig. 8: Schematic of the molecular architecture of plaque-associated axonal spheroids.

Proximity labeling proteomics reveals proteins associated with various subcellular organelles, the ubiquitin–proteosome system and cytoskeleton. These proteins and their signaling pathways are linked to biological functions, including protein turnover and vesicle fusion (green box); cytoskeletal dynamics (yellow box); lipid localization and transport (red box); and others (gray box). Highlighted here are selected newly identified and validated proteins, alongside those previously known to be enriched in PAASs, such as lysosomal proteins LAMP1 (ref. 4), cathepsin B and D14, RAGC14 and PLD3 (refs. 47,48); autophagosome protein ATG9A112; endoplasmic reticulum proteins RTN3 (ref. 112) and RTN1 (ref. 113); cytoskeletal neurofilament protein114; microtubule protein TUBB3 (ref. 20); synaptic proteins synaptophysin5 and VAMP2 (ref. 14); as well as APP31, Tau (MAPT)26 and ubiquitin71,112 (Supplementary Table 2).