Epilepsy: Neuroinflammation, neurodegeneration, and APOE genotype

Orwa Aboud, Robert E. Mrak, Frederick Boop, W. Sue T. Griffin

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Precocious development of Alzheimer-type neuropathological changes in epilepsy patients, especially in APOE ε4,4 carriers is well known, but not the ways in which other APOE allelic combinations influence this outcome. Frozen and paraffin-embedded tissue samples resected from superior temporal lobes of 92 patients undergoing temporal lobectomies as a treatment for medication-resistant temporal lobe epilepsy were used in this study. To determine if epilepsy-related changes reflect those in another neurological condition, analogous tissue samples harvested from 10 autopsy-verified Alzheimer brains, and from 10 neurologically and neuropathologically normal control patients were analyzed using immunofluorescence histochemistry, western immunoblot, and real-time PCR to determine genotype effects on neuronal number and size, neuronal and glial expressions of amyloid β (Aβ) precursor protein (βAPP), Aβ, apolipoprotein E (ApoE), S100B, interleukin-1α and β, and α and β secretases; and on markers of neuronal stress, including DNA/RNA damage and caspase 3 expression. Results: Allelic combinations of APOE influenced each epilepsy-related neuronal and glial response measured as well as neuropathological change. APOE ε3,3 conferred greatest neuronal resilience denoted as greatest production of the acute phase proteins and low neuronal stress as assessed by DNA/RNA damage and caspase-3 expression. Among patients having an APOE ε2 allele, none had Aβ plaques; their neuronal sizes, like those with APOE ε3,3 genotype were larger than those with other genotypes. APOE ε4,4 conferred the weakest neuronal resilience in epilepsy as well as in Alzheimer patients, but there were no APOE genotype-dependent differences in these parameters in neurologically normal patients. Conclusions: Our findings provide evidence that the strength of the neuronal stress response is more related to patient APOE genotype than to either the etiology of the stress or to the age of the patient, suggesting that APOE genotyping may be a useful tool in treatment decisions.

Original languageEnglish (US)
Article number41
JournalActa Neuropathologica Communications
Volume2
Issue number1
DOIs
StatePublished - Jan 27 2014

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Epilepsy
Genotype
Serum Amyloid A Protein
Neuroglia
Caspase 3
DNA Damage
RNA
Amyloid Precursor Protein Secretases
Temporal Lobe Epilepsy
Acute-Phase Proteins
Staphylococcal Protein A
Apolipoproteins E
Temporal Lobe
Interleukin-1
Paraffin
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
Autopsy
Western Blotting
Alleles

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Epilepsy : Neuroinflammation, neurodegeneration, and APOE genotype. / Aboud, Orwa; Mrak, Robert E.; Boop, Frederick; Griffin, W. Sue T.

In: Acta Neuropathologica Communications, Vol. 2, No. 1, 41, 27.01.2014.

Research output: Contribution to journalArticle

Aboud, Orwa ; Mrak, Robert E. ; Boop, Frederick ; Griffin, W. Sue T. / Epilepsy : Neuroinflammation, neurodegeneration, and APOE genotype. In: Acta Neuropathologica Communications. 2014 ; Vol. 2, No. 1.
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