APP and early-onset autosomal dominant Alzheimer disease: Of particular relevance to the current study, tau aggregation is also an invariant pathology in certain lysosomal disorders, most notably Niemann Pick Type C. The prototypic “secondary” tauopathy is, of course, Alzheimer's disease in which abnormal amyloid precursor protein processing and beta-amyloid accumulation is considered the inciting event, and tau aggregation an essential downstream mediator of neurotoxicity [55].