Temporal lobar predominance of TDP-43 neuronal cytoplasmic inclusions in Alzheimer disease.
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.
Hu
William T
WT
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Josephs
Keith A
KA
Knopman
David S
DS
Boeve
Bradley F
BF
Dickson
Dennis W
DW
Petersen
Ronald C
RC
Parisi
Joseph E
JE
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology*
D004268:DNA-Binding Proteins