Ma. Marques et al., A THROMBIN CLEAVAGE FRAGMENT OF APOLIPOPROTEIN-E EXHIBITS ISOFORM-SPECIFIC NEUROTOXICITY, NeuroReport, 7(15-17), 1996, pp. 2529-2532
A 22 kDa fragment of apoE containing a putative cytotoxi domain was id
entified 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 ne
urons in culture and that the E4-derived fragment is significantly mor
e toxic than the fragment derived from the E3 isoform. These results s
uggest that proteolytic fragments of apoE may play a direct role in th
e pathology associated with AD and other diseases in which apoE has be
en implicated.