title: Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar degeneration?
abstract: OBJECTIVE
  To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD).
  
  
  METHODS
  In this case-control study, we identified all subjects with a pathologic diagnosis of FTLD with TDP-43 immunoreactive inclusions (FTLD-TDP) and at least one volumetric head MRI scan (n = 42). In each case we applied published criteria for subclassification of FTLD-TDP into FTLD-TDP types 1-3. Voxel-based morphometry was used to compare subjects with each of the different FTLD-TDP types to age- and gender-matched normal controls (n = 30). We also assessed different pathologic and genetic variants within, and across, the different types.
  
  
  RESULTS
  Twenty-two subjects were classified as FTLD-TDP type 1, 9 as type 2, and 11 as type 3. We identified different patterns of atrophy across the types with type 1 showing frontotemporal and parietal atrophy, type 2 predominantly anterior temporal lobe atrophy, and type 3 predominantly posterior frontal atrophy. Within the FTLD-TDP type 1 group, those with a progranulin mutation had significantly more lateral temporal lobe atrophy than those without. All type 2 subjects were diagnosed with semantic dementia. Subjects with a pathologic diagnosis of FTLD with motor neuron degeneration had a similar pattern of atrophy, regardless of whether they were type 1 or type 3.
  
  
  CONCLUSIONS
  Although there are different patterns of atrophy across the different FTLD-TDP types, it appears that genetic and pathologic factors may also affect the patterns of atrophy.
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Whitwell
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
authors.forename: J E
authors.initials: JE
authors.lastname: Parisi
authors.forename: M L
authors.initials: ML
authors.lastname: Senjem
authors.forename: D S
authors.initials: DS
authors.lastname: Knopman
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: R
authors.initials: R
authors.lastname: Rademakers
authors.forename: M
authors.initials: M
authors.lastname: Baker
authors.forename: R C
authors.initials: RC
authors.lastname: Petersen
authors.forename: D W
authors.initials: DW
authors.lastname: Dickson
authors.forename: K A
authors.initials: KA
authors.lastname: Josephs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000145:classification / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins