M.A.Marques, M. Tolar, J.A.K. Harmony and K.A. Crutcher, A
thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific
neurotoxicity, NeuroReport, 7:2529-2532 (1996).
Abstract
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.
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