Experimental studies on tau derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices, have demonstrated that the presence of Aβ accelerates the production of a rare soluble species of high-molecular-weight (HMW) hyperphosphorylated tau, which appears to be a competent substrate for the intercellular spread [178]. This evidence concerns the gene MAPT and Alzheimer disease.