We present several lines of evidence for this interaction, (i) positive interaction in two different yeast two-hybrid systems, (ii) association found by co-immunoprecipitation, (iii) axotrophin association with tau protein aggregates in Alzheimer's disease, (iv) altered axotrophin expression/localization in tau knock-out mice and (v) tau mono-ubiquitination by axotrophin in vitro. The gene discussed is MAPT; the disease is early-onset autosomal dominant Alzheimer disease.