Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro 1.0.0

Among the seven antibodies, Tau13 and 6C5 most efficiently removed tau (>85% reduction) from rTg4510 brain extracts on immunodepletion (Figure 2A). HT7 showed an intermediate effect (72% reduction), whereas the other four antibodies (40E8, 4E4, p396, and Tau46) removed only a small fraction of tau (5.6%, 16.6%, 8.4%, and 18% reductions, respectively) (Figure 2A). PubMed:28408124

The 40E8, 4E4, and p396 antibodies also reduced neuronal tau uptake by 40% to 80%, despite their low-immunodepletion efficiency (Figure 2). This finding suggests that they interacted with tau species that are prone to cellular uptake, which account for only a small fraction of all soluble tau species in the brain extract. Notably, Tau46 had little effect on tau uptake (Figure 2, B and C). PubMed:28408124

Tau13, 6C5, and HT7 efficiently depleted tau from the AD HMW fraction (97%, 82%, and 72%, respectively), whereas the other four antibodies (40E8, 4E4, p396, and Tau46) removed only a small fraction of tau (33%, 4.7%, 22%, and 21% reductions, respectively) (Figure 4A). PubMed:28408124

In the tau uptake assay, 6C5 most effectively reduced tau uptake by immunodepletion (75% reduction) (Figure 4, B and C). Tau13 and HT7 showed intermediate effects (55% and 47% reductions, respectively) (Figure 4, B and C). The 40E8, p396, and 4E4 antibodies also reduced neuronal tau uptake (65%, 53%, and 47% reductions, respectively), despite their low immunodepletion efficiency (Figure 4). PubMed:28408124