A morphometric study of the spatial patterns of TDP-43 immunoreactive neuronal inclusions in frontotemporal lobar degeneration (FTLD) with progranulin (GRN) mutation
Richard A. Armstrong1 and Nigel J. Cairns2
1Vision Sciences, Aston University, Birmingham, UK and 2Departments of Neurology and Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Offprint requests to: R.A. Armstrong, Vision Sciences, Aston University, Birmingham, B4 7ET, UK. Email: R.A.Armstrong@aston.ac.uk
Summary. Mutations of the progranulin (GRN) gene are a major cause of familial frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP). We studied the spatial patterns of TDP-43 immunoreactive neuronal cytoplasmic inclusions (NCI) and neuronal intranuclear inclusions (NII) in histological sections of the frontal and temporal lobe in eight cases of FTLD-TDP with GRN mutation using morphometric methods and spatial pattern analysis. In neocortical regions, the NCI were clustered and the clusters were regularly distributed parallel to the pia mater; 58% of regions analysed exhibiting this pattern. The NII were present in regularly distributed clusters in 35% of regions but also randomly distributed in many areas. In neocortical regions, the sizes of the regular clusters of NCI and NII were 400-800 µm, approximating to the size of the modular columns of the cortico-cortical projections, in 31% and 36% of regions respectively. The NCI and NII also exhibited regularly spaced clustering in sectors CA1/2 of the hippocampus and in the dentate gyrus. The clusters of NCI and NII were not spatially correlated. The data suggest degeneration of the cortico-cortical and cortico-hippocampal pathways in FTLD-TDP with GRN mutation, the NCI and NII affecting different clusters of neurons. Histol Histopathol 26, 185-190 (2011)
Key words: Frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP), TAR DNA-binding protein (TDP-43), Progranulin (GRN) mutation, Spatial topography