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

Keith A. Vossel, Nga Bien-Ly, Aubrey Bernardo, Katya Rascovsky, Anna Karydas, Gil D. Rabinovici, Manu Sidhu, Eric J. Huang, Bruce L. Miller, Yadong Huang, William W. Seeley

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)295-301
Number of pages7
Issue number3
StatePublished - Jul 4 2013


  • Apolipoprotein E
  • Frontotemporal dementia
  • Motor neuron disease
  • Neuropathology
  • TDP-43

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