Figure 4.

Exosomes from human CSF contain detectable amounts of full-length, aggregation-competent tau. (A) CSF samples from six healthy controls were processed by serial centrifugation, as described in Figure 3A. Free tau was measured in CSF in 10,000 g supernatant (blue) 100,000 g supernatant (red), and the 100,000 g pellet (purple). The majority of tau is free-floating, while a small amount of tau is recovered in the exosomal pellet of 4 out of 6 samples. Values represent the mean of technical replicates. (B,C) Two pools of CSF, designated Pool A and Pool B, were processed as above and the 2,000 g supernatants (blue) 100,000 g supernatants (red), and 100,000 g pellets (purple) analyzed using our mid-region ELISA (B) and FL Simoa assay (C). Concentrations represent the amount of analyte present in 1 mL of starting cerebrospinal fluid (CSF) and are corrected to account for dilutions incurred during the various processing steps. Results in (A) represent the mean of two technical replicates, and results in (B,C) indicate the mean ± SD of technical replicates of two independent experiments.