title: A quantitative study of the neuropathology of 32 sporadic and familial cases of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP).
abstract: OBJECTIVE
  To further characterize the neuropathology of the heterogeneous molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP).
  
  
  METHODS
  We quantified the neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe using a phosphorylation-independent TDP-43 antibody in 32 cases of FTLD-TDP comprising sporadic and familial cases, with associated pathology such as hippocampal sclerosis (HS) or Alzheimer's disease (AD), and four neuropathological subtypes using TDP-43 immunohistochemistry. Analysis of variance (anova) was used to compare differences between the various groups of cases.
  
  
  RESULTS
  These data from FTLD-TDP cases demonstrate quantitative differences in pathological features between: (i) regions of the frontal and temporal lobe; (ii) upper and lower cortex; (iii) sporadic and progranulin (GRN) mutation cases; (iv) cases with and without AD or HS; and (v) between assigned subtypes.
  
  
  CONCLUSIONS
  The data confirm that the dentate gyrus is a major site of neuropathology in FTLD-TDP and that most laminae of the cerebral cortex are affected. GRN mutation cases are quantitatively different from sporadic cases, while cases with associated HS and AD have increased densities of dystrophic neurites and abnormally enlarged neurones respectively. There is little correlation between the subjective assessment of subtypes and the more objective quantitative data.
authors.affiliation: Vision Sciences, Aston University, Birmingham, UK. r.a.armstrong@aston.ac.uk
authors.forename: R A
authors.initials: RA
authors.lastname: Armstrong
authors.forename: D
authors.initials: D
authors.lastname: Carter
authors.forename: N J
authors.initials: NJ
authors.lastname: Cairns
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000077153:Progranulins; D012598:Sclerosis / Q000150:complications
chemical_list: D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins