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Furthermore, the E4 isoform of the 22 kDa fragment is significantly more toxic than the same fragment derived from the E3 isoform, suggesting the possibility of a direct role of apoE-associated neurotoxicity in the pathophysiology of Alzheimer\u2019s disease. In the present study, the potential role of cell surface receptors in mediating neurotoxicity was assessed by using a variety of agents that should block the heparin-binding and receptor-binding activity of apoE. Effective inhibitors of neurotoxicity of both the apoE peptides and the apoE fragment include heparin, heparan sulfate, sodium chlorate and heparinase, the low-density lipoprotein (LDL) receptor-related protein receptor-associated protein, and a polyclonal anti-LDL receptor-related protein antibody. These results suggest that the neurotoxicity of the 22 kDa thrombin cleavage fragment of apoE and related peptides is receptor-mediated, and that the most likely candidate receptor is a heparan sulfate proteoglycan\u2013LDL receptor-related protein complex.<\/jats:p>","DOI":"10.1523\/jneurosci.17-15-05678.1997","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T22:29:14Z","timestamp":1522967354000},"page":"5678-5686","source":"Crossref","is-referenced-by-count":95,"title":["Neurotoxicity of the 22 kDa Thrombin-Cleavage Fragment of Apolipoprotein E and Related Synthetic Peptides Is Receptor-Mediated"],"prefix":"10.1523","volume":"17","author":[{"given":"Martin","family":"Tolar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos A.","family":"Marques","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith A. 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