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Temporal lobar predominance of TDP-43 neuronal cytoplasmic inclusions in Alzheimer disease

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Abstract

TAR DNA binding protein-43 (TDP-43) immunoreactive neuronal inclusions are detected in 20–30% of Alzheimer disease (AD) brains, but the distribution of this pathology has not been rigorously studied. In this report, we describe region-specific distribution and density of TDP-43 positive neuronal cytoplasmic inclusions (NCIs) in clinically demented individuals with high probability AD pathology, all with Braak neurofibrillary tangle stages of V or VI. Sections of hippocampus, amygdala, as well as temporal, frontal, and parietal neocortex, were analyzed with TDP-43 immunohistochemistry, and the density of NCIs was assessed using a semiquantitative scoring method. Of the 29 cases, six had TDP-43 positive NCIs in the amygdala only and seven had TDP-43 inclusions restricted to amygdala and hippocampus. In 16 cases, TDP-43 immunoreactivity was more widespread, affecting temporal, frontal or parietal neocortex. These findings indicate that medial temporal lobe limbic structures are vulnerable to TDP-43 pathology in advanced AD, and that the amygdala appears to be the most susceptible region. The distribution of the lesions in this cross-sectional analysis may suggest a progression of TDP-43 pathology in AD, with limbic structures in the medial temporal lobe affected first, followed by higher order association cortices.

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Acknowledgments

This study was supported by NIH grants P50 AG16574, U01 AG06786, and K12 HD49078 (to KAJ) and the generous support of the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation, USA.

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Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    William T. Hu, Keith A. Josephs, David S. Knopman, Bradley F. Boeve & Ronald C. Petersen

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA

    William T. Hu & Joseph E. Parisi

  3. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA

    Dennis W. Dickson

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  1. William T. Hu
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  2. Keith A. Josephs
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  3. David S. Knopman
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  4. Bradley F. Boeve
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  5. Dennis W. Dickson
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  6. Ronald C. Petersen
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  7. Joseph E. Parisi
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Correspondence to Joseph E. Parisi.

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Hu, W.T., Josephs, K.A., Knopman, D.S. et al. Temporal lobar predominance of TDP-43 neuronal cytoplasmic inclusions in Alzheimer disease. Acta Neuropathol 116, 215–220 (2008). https://doi.org/10.1007/s00401-008-0400-4

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  • DOI: https://doi.org/10.1007/s00401-008-0400-4

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