Cautious interpretation of the results is warranted in relation to findings in aged post-mortem DS samples: virtually all DS individuals have omnipresent AD-pathology (i.e. Aβ plaques and tau tangles) in their brain from the age of 40 years onwards (Mann, 1988), complicating the comparison between findings in DS and Ts65Dn mice that do not model human AD neuropathology in DS. Here, MAPT is linked to Alzheimer disease.