Mutation increment K281 in MAPT causes Pick's disease

Two siblings with deletion mutation increment 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 increment K281 causes Pick's disease.

Automated summary

Two siblings with a deletion mutation at K281 of MAPT gene developed frontotemporal dementia. Autopsy revealed numerous hyperphosphorylated 3R Tau inclusions in neurons and glial cells of the neocortex and some subcortical regions, including the hippocampus, caudate/putamen, and globus pallidus. These inclusions were argyrophilic with Bodian silver staining but not Gallyas-Braak silver staining. They were not labeled by an antibody specific for tau phosphorylation at S262 and/or S356. Luminescent conjugated oligothiophene HS-84 stained the inclusions, but bTVBT4 did not. Electron cryo-microscopy showed that the core of tau filaments consisted of residues K254-F378 of 3R Tau and was indistinguishable from Pick's disease. We conclude that the MAPT mutation at K281 leads to Pick's disease.