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Acta Neuropathol. 2008 Aug;116(2):215-20. doi: 10.1007/s00401-008-0400-4. Epub 2008 Jul 1.

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

Author information

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

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.

PMID:
18592255
PMCID:
PMC3404722
DOI:
10.1007/s00401-008-0400-4
[Indexed for MEDLINE]
Free PMC Article

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