Fig. 1: Pathogenic αSyn aggregates accumulate within lysosomes of aged Tg-αSyn^A53T mice.

Lysosomes were isolated from 6-month-old Tg-αSyn^A53T mouse brains via Percoll gradient centrifugation of the heavy organelle fraction—which contained peroxisomes, heavy lysosomes loaded in vivo with dextran-70, and mitochondria swollen ex vivo by CaCl₂. a Lysosome (dextranosome) enrichment was determined by immunoblotting for markers of indicated organelles, compared to the respective levels in the total lysate input. Membrane-matched dot blots (β-Actin = loading control) are separated by dashed lines. b Left panels—Activities of enzymes contained within lysosomes (cathepsin-D), mitochondria (citrate synthase), and peroxisomes (catalase) were measured, testing for isolation of intact organelles. Right panel—Summary graph of enzyme activity present in the combined “lysosomal fractions” (fractions 8–10). c Top panels—Levels in each Percoll gradient fraction of pathogenic αSyn species: Aggregated (αSyn Aggr), aggregates phosphorylated at Ser129 (αSyn^pSer129 Aggr), filamentous (αSyn^Fila), and amyloid-type (αSyn^Amyl). Bottom panel—Summary graph of these αSyn species present in the combined “lysosomal fractions” (fractions 8–10). (n = 3). All data are shown as means ± SEM, where “n” represents mouse brains.