Acta Neuropathologica

, 116:215

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


  • William T. Hu
    • Department of NeurologyMayo Clinic
    • Department of Laboratory Medicine and PathologyMayo Clinic
  • Keith A. Josephs
    • Department of NeurologyMayo Clinic
  • David S. Knopman
    • Department of NeurologyMayo Clinic
  • Bradley F. Boeve
    • Department of NeurologyMayo Clinic
  • Dennis W. Dickson
    • Department of NeuroscienceMayo Clinic
  • Ronald C. Petersen
    • Department of NeurologyMayo Clinic
    • Department of Laboratory Medicine and PathologyMayo Clinic
Original Paper

DOI: 10.1007/s00401-008-0400-4

Cite this article as:
Hu, W.T., Josephs, K.A., Knopman, D.S. et al. Acta Neuropathol (2008) 116: 215. doi:10.1007/s00401-008-0400-4


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.


AmygdalaFTLD-UFTLD-MNDFrontotemporal dementiaMotor neuron disease

Copyright information

© Springer-Verlag 2008