D T Ohm1, G Kim1, T Gefen1,2, A Rademaker1,3, S Weintraub1,2, E H Bigio1,4, M-M Mesulam1,5, E Rogalski1, C Geula1. 1. Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 2. Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 3. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 4. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 5. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Abstract
AIMS: Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. METHODS: Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. RESULTS: Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). CONCLUSIONS: White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy.
AIMS: Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with eitherAD or FTLD-TDP pathology. METHODS: Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. RESULTS: Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). CONCLUSIONS: White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy.
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: 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
Authors: Ione O C Woollacott; Christina E Toomey; Catherine Strand; Robert Courtney; Bridget C Benson; Jonathan D Rohrer; Tammaryn Lashley Journal: J Neuroinflammation Date: 2020-08-10 Impact factor: 8.322
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