Protein aggregation and dysfunction of the ubiquitin-proteasome system are hallmarks of many neurodegenerative diseases. Here, we address the elusive link between these phenomena by employing cryo-electron tomography to dissect the molecular architecture of protein aggregates within intact neurons at high resolution. We focus on the poly-Gly-Ala (poly-GA) aggregates resulting from aberrant translation of an expanded GGGGCC repeat in C9orf72, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. We find that poly-GA aggregates consist of densely packed twisted ribbons that recruit numerous 26S proteasome complexes, while other macromolecules are largely excluded. Proximity to poly-GA ribbons stabilizes a transient substrate-processing conformation of the 26S proteasome, suggesting stalled degradation. Thus, poly-GA aggregates may compromise neuronal proteostasis by driving the accumulation and functional impairment of a large fraction of cellular proteasomes. Display omitted •Neuronal C9orf72 poly-GA aggregates were analyzed by cryoelectron tomography•Poly-GA aggregates in neurons consist of planar twisted ribbons•Poly-GA aggregates recruit proteasomes while excluding other large macromolecules•Interactions with poly-GA aggregates lead to proteasome stalling Neuronal poly-GA aggregates linked to amyotrophic lateral sclerosis and frontotemporal dementia selectively sequester proteasomes.