APP and Alzheimer disease: Given the genetic evidence linking APP and its cleavage to AD, it was proposed that signalling of APP via DR6 (and possibly p75NTR) may in particular contribute to the initiation or progression of AD, either alone or in combination with other proposed APP-dependent mechanisms, such as amyloid β-peptide (Aβ) toxicity [5, 6] or effects of the APP intracellular domain [7].