title: A morphometric study of the spatial patterns of TDP-43 immunoreactive neuronal inclusions in frontotemporal lobar degeneration (FTLD) with progranulin (GRN) mutation.
abstract: Mutations of the progranulin (GRN) gene are a major cause of familial frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43 kDa (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.
authors.affiliation: Vision Sciences, Aston University, Birmingham, UK. R.A.Armstrong@aston.ac.uk
authors.forename: Richard A
authors.initials: RA
authors.lastname: Armstrong
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size; D000077153:Progranulins; D011498:Protein Precursors; D057177:TDP-43 Proteinopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D011498:Protein Precursors