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TDP-43 Pathologic Lesions and Clinical Phenotype in Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions
Murray Grossman, MD;
Elisabeth M. Wood, MS;
Peachie Moore, BA;
Manuela Neumann, MD, PhD;
Linda Kwong, PhD;
Mark S. Forman, MD, PhD;
Christopher M. Clark, MD;
Leo F. McCluskey, MD;
Bruce L. Miller, MD;
Virginia M.-Y. Lee, PhD, MBA;
John Q. Trojanowski, MD, PhD
Arch Neurol. 2007;64(10):1449-1454.
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.
Author Affiliations: Departments of Neurology (Drs Grossman, Clark, and McCluskey and Ms Moore) and Pathology and Laboratory Medicine (Ms Wood and Drs Kwong, Forman, Lee, and Trojanowski), Center for Neurodegenerative Disease Research (Ms Wood and Drs Neumann, Kwong, Forman, Lee, and Trojanowski), and Alzheimer's Disease Center (Dr Clark), University of Pennsylvania School of Medicine, Philadelphia; Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich, Munich, Germany (Dr Neumann); and Department of Neurology, University of California, San Francisco (Dr Miller).
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Distinct Antemortem Profiles in Patients With Pathologically Defined Frontotemporal Dementia
Grossman et al.
Arch Neurol 2007;64:1601-1609.
ABSTRACT
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