Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar degeneration?

Neurology. 2010 Dec 14;75(24):2212-20. doi: 10.1212/WNL.0b013e31820203c2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atrophy
  • Brain / metabolism*
  • Brain / pathology*
  • Case-Control Studies
  • DNA-Binding Proteins / classification
  • DNA-Binding Proteins / metabolism*
  • Female
  • Frontal Lobe / metabolism
  • Frontal Lobe / pathology
  • Frontotemporal Lobar Degeneration / metabolism*
  • Frontotemporal Lobar Degeneration / pathology*
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Parietal Lobe / metabolism
  • Parietal Lobe / pathology
  • Risk Factors
  • Temporal Lobe / metabolism
  • Temporal Lobe / pathology


  • DNA-Binding Proteins