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Neurocase. 2013;19(3):295-301. doi: 10.1080/13554794.2012.667124. Epub 2012 Apr 18.

ApoE and TDP-43 neuropathology in two siblings with familial FTLD-motor neuron disease.

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1
Department of Neurology, University of California, San Francisco, CA, USA.

Abstract

Frontotemporal lobar degeneration with motor neuron disease (FTLD-MND) is characterized by neuronal cytoplasmic inclusions containing TDP-43. Apolipoprotein E4 (apoE4), derived from the apoE ϵ4 allele, enhances brain atrophy in FTLD through unknown mechanisms. Here, we studied two siblings with C9ORF72-linked familial FTLD-MND, an apoE ϵ4 homozygote and an apoE ϵ3 homozygote. The apoE ϵ4 homozygote had more cognitive-behavioral symptoms, fronto-insulo-temporal atrophy, and apoE fragments and aggregates in the anterior cingulate cortex. ApoE formed complexes with TDP-43 that were more abundant in the apoE ϵ4 homozygote. Although differences seen in a sibling pair could arise due to chance, these findings raise the possibility that apoE4 exacerbates brain pathology in FTLD through formation of neurotoxic apoE fragments and interactions with TDP-43.

PMID:
22512241
PMCID:
PMC3655113
DOI:
10.1080/13554794.2012.667124
[Indexed for MEDLINE]
Free PMC Article
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