I am trying to isolate exosomes from human serum. I tested two different methods: precipitation with ExoQuick solution and ultracentrifugation at 100,000 × g. However, I couldn't obtain a clean exosome proteome with either method. After isolation, I ran SDS-PAGE and then performed an LC-MS/MS analyses to detect exosomal markers. Unfortunately, I mainly detected abundant serum proteins such as immunoglobulins and apolipoproteins, instead of exosomal markers. What would you recommend to reduce these serum proteins and obtain a more enriched exosome protein profile? Any suggestions would be nice.