The conformational templating process for amplification of AD brain-derived tau seeds utilizes purified recombinant K18 (4R) and K19 (3R) tau substrates or their chimeras [163,164], and at the same substrate concentrations, the AD brain-derived tau seeds preferentially amplify with K18 (4R) substrate and demonstrate end point sensitivity up to 109 dilution of the brain tissue [10,165,166]. Here, MAPT is linked to Alzheimer disease.