TDP-43 pathologic lesions and clinical phenotype in frontotemporal lobar degeneration with ubiquitin-positive inclusions.

BACKGROUND

TDP-43 is a major ubiquitinated disease protein in the pathologic condition of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U).

OBJECTIVE

To investigate the demographic, clinical, and neuropsychological features associated with subtypes of FTLD-U with TDP-43 inclusions (FTLD-U/TDP-43).

DESIGN

Retrospective clinical-pathologic study.

SETTING

Academic medical center. Patients Twenty-three patients with histopathologically proven FTLD-U.

MAIN OUTCOME MEASURES

Demographic, symptom, neuropsychological, and autopsy characteristics.

RESULTS

There are notably different clinical and neuropsychological patterns of impairment in FTLD-U subtypes. Patients with FTLD-U/TDP-43 characterized by numerous neuronal intracytoplasmic inclusions have shorter survival; patients with FTLD-U/TDP-43 featuring numerous neurites have difficulty with object naming; and patients with FTLD-U/TDP-43 in whom neuronal intranuclear inclusions are present have substantial executive deficits. There are also different anatomical distributions of ubiquitin pathologic features in FTLD-U subgroups, consistent with their cognitive deficits.

CONCLUSION

Distinct TDP-43 profiles may affect clinical phenotypes differentially in patients with FTLD-U.