Recently, Nikolaev and colleagues[10] reported that the N-terminal fragment of amyloid precursor protein (N-APP) may act as a ligand of DR6 and trigger axon pruning and neurodegeneration via caspase 6, suggesting a role for this receptor in the neurodegeneration observed in Alzheimer’s disease (AD; for review see[11]). Here, TNFRSF21 is linked to early-onset autosomal dominant Alzheimer disease.