Mutation ∆K281 in MAPT causes Pick’s disease
Manuel Schweighauser, Holly J. Garringer, Therése Klingstedt, K. Peter R. Nilsson, Masami Masuda‐Suzukake, Jill R. Murrell, Shannon L. Risacher, Rubén Vidal, Sjors H. W. Scheres, Michel Goedert, Bernardino Ghetti, Kathy L. Newell
Abstract
Two siblings with deletion mutation ∆K281 in MAPT developed frontotemporal dementia. At autopsy, numerous inclusions of hyperphosphorylated 3R Tau were present in neurons and glial cells of neocortex and some subcortical regions, including hippocampus, caudate/putamen and globus pallidus. The inclusions were argyrophilic with Bodian silver, but not with Gallyas-Braak silver. They were not labelled by an antibody specific for tau phosphorylated at S262 and/or S356. The inclusions were stained by luminescent conjugated oligothiophene HS-84, but not by bTVBT4. Electron cryo-microscopy revealed that the core of tau filaments was made of residues K254-F378 of 3R Tau and was indistinguishable from that of Pick's disease. We conclude that MAPT mutation ∆K281 causes Pick's disease.