At 70% of the TSD, despite similar absolute amounts of total PrP remaining after immuno-depletion when compared to 30% and 50% of the TSD, only dM1000 from 70% caused PTP impairment, with modest PK treatment of the complementary 60% of total PrP captured in the immuno-precipitated pellets able to completely abrogate any acute synaptotoxicity. The gene discussed is PRNP; the disease is Tay-Sachs disease.