Patterns of microglial cell activation in frontotemporal lobar degeneration. Issue 6 (October 2014)

• Record Type: Journal Article
• Authors: Lant, Suzannah B.; Robinson, Andrew C.; Thompson, Jennifer C.; Rollinson, Sara; Pickering‐Brown, Stuart; Snowden, Julie S.; Davidson, Yvonne S.; Gerhard, Alexander; Mann, David M. A.
• Is Part Of: Neuropathology & applied neurobiology. Volume 40:Issue 6(2014)
• Page Start: 686
• Page End: 696
• Publication Date: 2014-10
• Subjects: Nervous system -- Diseases -- Pathology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/nan.12092
• Languages: English
• ISSNs: 0305-1846

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="nan12092-sec-0001" sec-type="section"> <title>Aims</title> <p>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 <italic>in vivo</italic> using PET ligand [11C](R)‐PK11195 in order to differentiate cases of FTLD according to histological subtype.</p> </sec> <sec id="nan12092-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="nan12092-sec-0003" sec-type="section"> <title>Results</title> <p>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‐<italic>MAPT</italic> than in other genetic (<italic>GRN</italic>, <italic>C9ORF</italic><italic>72</italic>) or non‐genetic forms of FTLD.</p> </sec> <sec id="nan12092-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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 <italic>MAPT</italic>, with a relatively intense signal in this region in PET studies using [11C](R)‐PK11195 as microglial cell marker could indicate the presence of <italic>MAPT</italic> mutation<italic> in vivo</italic>.</p> </sec> </abstract>