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Transactive Response DNA-Binding Protein 43 Burden in Familial Alzheimer Disease and Down Syndrome
Carol F. Lippa, MD;
Andrea L. Rosso, MPH;
Lauren D. Stutzbach, BA;
Manuela Neumann, MD;
Virginia M.-Y. Lee, PhD;
John Q. Trojanowski, MD, PhD
Arch Neurol. 2009;66(12):1483-1488.
Objective To assess the transactive response DNA-binding protein 43 (TDP-43) burden in familial forms of Alzheimer disease (FAD) and Down syndrome (DS) to determine whether TDP-43 inclusions are also present.
Design Using standard immunohistochemical techniques, we examined brain tissue samples from 42 subjects with FAD and 14 with DS.
Results We found pathological TDP-43 aggregates in 14.0% of participants (6 of 42 and 2 of 14 participants with FAD and DS, respectively). In both FAD and DS, TDP-43 immunoreactivity did not colocalize with neurofibrillary tangles. Occasionally participants with FAD or DS had TDP-43–positive neuropil threads or dots. Overall, the amygdala was most commonly affected, followed by the hippocampus, with no TDP-43 pathology in neocortical regions. A similar distribution of TDP-43 inclusions is seen in sporadic Alzheimer disease, but it differs from that seen in amyotrophic lateral sclerosis and frontotemporal dementia.
Conclusions Transactive response DNA-binding protein 43 pathology occurs in FAD and DS, similar to that observed in sporadic Alzheimer disease. Thus, pathological TDP-43 may contribute the cognitive impairments in familial and sporadic forms of Alzheimer disease.
Author Affiliations: Drexel University College of Medicine Philadelphia, Philadelphia, Pennsylvania (Dr Lippa and Ms Rosso); Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (Ms Stutzbach, and Drs Lee and Trojanowski); and Institute of Neuropathology, University Hospital of Zürich, Zürich, Switzerland (Dr Neumann).
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