Projection neurons (not only those of the locus coeruleus) are sturdy and can survive for a lifetime despite the existence of Alzheimer-related abnormal tau. Currently, little understood mechanisms most probably exist that enable neurons to fulfill their general functions even when severe tau pathology is present. The proclivity of predisposed neuronal types to develop abnormal tau may be intrinsic to the human brain. However, the tempo of disease progression reveals considerable individual differences, thereby offering opportunities to study conditions that may modify disease progression.