AIMS: Pathological heterogeneity within patients with frontotemporal lobar degeneration (FTLD) in general precludes the accurate assignment of diagnostic subtype in life. The aim of this study was to assess the extent of microglial cell activation in FTLD in order to determine whether it might be possible to employ this as a diagnostic marker in vivo using PET ligand [11C](R)-PK11195 in order to differentiate cases of FTLD according to histological subtype. METHODS: The distribution and extent of microglial cell activation was assessed semi-quantitatively in cortical grey and subcortical white matter of CD68 immunostained sections of frontal and temporal cortex from 78 pathologically confirmed cases of FTLD, 13 of Alzheimer's disease (AD) and 13 controls. RESULTS: Significantly higher levels of microglial cell activation than controls occurred in all four regions in FTLD, and in three of the four regions in AD. Microglial activation was greater in frontal subcortical white matter in FTLD than AD, whereas it was higher in temporal cortical grey matter in AD than FTLD. Microglial cell activation was significantly higher in temporal subcortical white matter in FTLD-MAPT than in other genetic (GRN, C9ORF72) or non-genetic forms of FTLD. CONCLUSIONS: The present study suggests that high levels of microglial cell involvement in temporal lobe (subcortical white matter) might serve as a marker of inherited FTLD associated with intronic mutations in MAPT, with a relatively intense signal in this region in PET studies using [11C](R)-PK11195 as microglial cell marker could indicate the presence of MAPT mutation in vivo.
AIMS: Pathological heterogeneity within patients with frontotemporal lobar degeneration (FTLD) in general precludes the accurate assignment of diagnostic subtype in life. The aim of this study was to assess the extent of microglial cell activation in FTLD in order to determine whether it might be possible to employ this as a diagnostic marker in vivo using PET ligand [11C](R)-PK11195 in order to differentiate cases of FTLD according to histological subtype. METHODS: The distribution and extent of microglial cell activation was assessed semi-quantitatively in cortical grey and subcortical white matter of CD68 immunostained sections of frontal and temporal cortex from 78 pathologically confirmed cases of FTLD, 13 of Alzheimer's disease (AD) and 13 controls. RESULTS: Significantly higher levels of microglial cell activation than controls occurred in all four regions in FTLD, and in three of the four regions in AD. Microglial activation was greater in frontal subcortical white matter in FTLD than AD, whereas it was higher in temporal cortical grey matter in AD than FTLD. Microglial cell activation was significantly higher in temporal subcortical white matter in FTLD-MAPT than in other genetic (GRN, C9ORF72) or non-genetic forms of FTLD. CONCLUSIONS: The present study suggests that high levels of microglial cell involvement in temporal lobe (subcortical white matter) might serve as a marker of inherited FTLD associated with intronic mutations in MAPT, with a relatively intense signal in this region in PET studies using [11C](R)-PK11195 as microglial cell marker could indicate the presence of MAPT mutation in vivo.
Authors: Hideyuki Takahashi; Zoe A Klein; Sarah M Bhagat; Adam C Kaufman; Mikhail A Kostylev; Tsuneya Ikezu; Stephen M Strittmatter Journal: Acta Neuropathol Date: 2017-01-09 Impact factor: 17.088
Authors: Ione O C Woollacott; Jennifer M Nicholas; Carolin Heller; Martha S Foiani; Katrina M Moore; Lucy L Russell; Ross W Paterson; Ashvini Keshavan; Jonathan M Schott; Jason D Warren; Amanda Heslegrave; Henrik Zetterberg; Jonathan D Rohrer Journal: Dement Geriatr Cogn Disord Date: 2020-04-28 Impact factor: 2.959
Authors: D T Ohm; G Kim; T Gefen; A Rademaker; S Weintraub; E H Bigio; M-M Mesulam; E Rogalski; C Geula Journal: Neuropathol Appl Neurobiol Date: 2018-05-17 Impact factor: 8.090
Authors: Cyril Pottier; Yingxue Ren; Ralph B Perkerson; Matt Baker; Gregory D Jenkins; Marka van Blitterswijk; Mariely DeJesus-Hernandez; Jeroen G J van Rooij; Melissa E Murray; Elizabeth Christopher; Shannon K McDonnell; Zachary Fogarty; Anthony Batzler; Shulan Tian; Cristina T Vicente; Billie Matchett; Anna M Karydas; Ging-Yuek Robin Hsiung; Harro Seelaar; Merel O Mol; Elizabeth C Finger; Caroline Graff; Linn Öijerstedt; Manuela Neumann; Peter Heutink; Matthis Synofzik; Carlo Wilke; Johannes Prudlo; Patrizia Rizzu; Javier Simon-Sanchez; Dieter Edbauer; Sigrun Roeber; Janine Diehl-Schmid; Bret M Evers; Andrew King; M Marsel Mesulam; Sandra Weintraub; Changiz Geula; Kevin F Bieniek; Leonard Petrucelli; Geoffrey L Ahern; Eric M Reiman; Bryan K Woodruff; Richard J Caselli; Edward D Huey; Martin R Farlow; Jordan Grafman; Simon Mead; Lea T Grinberg; Salvatore Spina; Murray Grossman; David J Irwin; Edward B Lee; EunRan Suh; Julie Snowden; David Mann; Nilufer Ertekin-Taner; Ryan J Uitti; Zbigniew K Wszolek; Keith A Josephs; Joseph E Parisi; David S Knopman; Ronald C Petersen; John R Hodges; Olivier Piguet; Ethan G Geier; Jennifer S Yokoyama; Robert A Rissman; Ekaterina Rogaeva; Julia Keith; Lorne Zinman; Maria Carmela Tartaglia; Nigel J Cairns; Carlos Cruchaga; Bernardino Ghetti; Julia Kofler; Oscar L Lopez; Thomas G Beach; Thomas Arzberger; Jochen Herms; Lawrence S Honig; Jean Paul Vonsattel; Glenda M Halliday; John B Kwok; Charles L White; Marla Gearing; Jonathan Glass; Sara Rollinson; Stuart Pickering-Brown; Jonathan D Rohrer; John Q Trojanowski; Vivianna Van Deerlin; Eileen H Bigio; Claire Troakes; Safa Al-Sarraj; Yan Asmann; Bruce L Miller; Neill R Graff-Radford; Bradley F Boeve; William W Seeley; Ian R A Mackenzie; John C van Swieten; Dennis W Dickson; Joanna M Biernacka; Rosa Rademakers Journal: Acta Neuropathol Date: 2019-02-09 Impact factor: 17.088