Patterns of microglial cell activation in frontotemporal lobar degeneration

Authors

  • Suzannah B. Lant,

    1. Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford, UK
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  • Andrew C. Robinson,

    1. Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford, UK
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  • Jennifer C. Thompson,

    1. Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford, UK
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  • Sara Rollinson,

    1. Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford, UK
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  • Stuart Pickering-Brown,

    1. Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford, UK
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  • Julie S. Snowden,

    1. Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford, UK
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  • Yvonne S. Davidson,

    1. Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford, UK
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  • Alexander Gerhard,

    1. Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford, UK
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  • David M. A. Mann

    Corresponding author
    1. Clinical and Cognitive Sciences Research Group, Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford, UK
    • Correspondence: David M. A. Mann, Clinical and Cognitive Neuroscience Research Group, University of Manchester, Salford Royal Foundation NHS Trust, Salford M6 8HD, UK. Tel: +44 161 206 2580; Fax: +44 161 206 0388; E-mail: david.mann@manchester.ac.uk

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Abstract

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.

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