PDK1 and Alzheimer disease: Aβ and other neurodegenerative ligands, such as prion protein, are known to induce the endocytosis of TACE and reduction in TACE activity via PDK1 activation in the AD brain.29 Aβ accumulation in the AD brain could conceivably reduce TACE activity, which leads to the reduction of p75NTR shedding and the reduction of the p75NTR-ECD level in the CSF of AD subjects.10