Schweighauser, ManuelGarringer, Holly J.Klingstedt, TheréseNilsson, K. Peter R.Masuda‑Suzukake, MasamiMurrell, Jill R.Risacher, Shannon L.Vidal, RubenScheres, Sjors H. W.Goedert, MichelGhetti, BernardinoNewell, Kathy L.2024-02-142024-02-142023Schweighauser M, Garringer HJ, Klingstedt T, et al. Mutation ∆K281 in MAPT causes Pick's disease. Acta Neuropathol. 2023;146(2):211-226. doi:10.1007/s00401-023-02598-6https://hdl.handle.net/1805/38477Two 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.en-USAttribution 4.0 InternationalTauFTDP-17TMAPT mutation ∆K281Pick’s diseaseSilver stainingLuminescent conjugated oligothiophenesElectron cryo-microscopyArticle