A thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific neurotoxicity

A 22 kDa fragment of apoE containing a putative cytotoxi domain was identified in postmortem human brain tissue and fresh CSF. This fragment is apparently equivalent to the major apoE thrombin cleavage product. In vitro toxicity assays demonstrate that the corresponding fragment derived from recombi...

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Bibliographic Details
Published inNeuroreport Vol. 7; no. 15-17; p. 2529
Main Authors Marques, M A, Tolar, M, Harmony, J A, Crutcher, K A
Format Journal Article
LanguageEnglish
Published England 04.11.1996
Subjects
Apolipoproteins E - metabolism
Apolipoproteins E - pharmacology
Blotting, Western
Brain - metabolism
Cell Count - drug effects
Dose-Response Relationship, Drug
Humans
Thrombin - pharmacology
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Summary:A 22 kDa fragment of apoE containing a putative cytotoxi domain was identified in postmortem human brain tissue and fresh CSF. This fragment is apparently equivalent to the major apoE thrombin cleavage product. In vitro toxicity assays demonstrate that the corresponding fragment derived from recombinantly expressed human apoE is toxic to primary neurons in culture and that the E4-derived fragment is significantly more toxic than the fragment derived from the E3 isoform. These results suggest that proteolytic fragments of apoE may play a direct role in the pathology associated with AD and other diseases in which apoE has been implicated.
ISSN:0959-4965
DOI:10.1097/00001756-199611040-00025