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

J. L. Whitwell, C. R. Jack, J. E. Parisi, M. L. Senjem, D. S. Knopman, B. F. Boeve, R. Rademakers, M. Baker, R. C. Petersen, D. W. Dickson, K. A. Josephs

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2212-2220
Number of pages9
Issue number24
StatePublished - Dec 14 2010

ASJC Scopus subject areas

  • Clinical Neurology


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