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Annals of Clinical & Laboratory Science 32:65-74 (2002)
© 2002 Association of Clinical Scientists

Isoform-specific Effect of Apolipoprotein E on Endocytosis of ß-Amyloid in Cultures of Neuroblastoma Cells

Kazuyoshi Yamauchi1, Minoru Tozuka1, Hiroya Hidaka1, Tetsuo Nakabayashi1, Mitsutoshi Sugano1 and Tsutomu Katsuyama2
1 Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan
2 Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan

Address correspondence to Kazuyoshi Yamauchi, Ph.D., Central Clinical Laboratories, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan; tel 81 263 37 2802; fax 81 263 34 5316; e-mail yamauchi{at}hsp.md.shinshu-u.ac.jp.

Investigation of the interactions of nerve cells with human apolipoprotein E (apoE), ß-amyloid (Aß), and their complex, which are known to be included in senile plaques, is necessary to clarify the functional role of apoE in the pathogenesis of Alzheimer’s disease. Using flow cytometric analysis, we investigated the isoform-specific effects of apoE on the endocytosis of Aß in cultured neuroblastoma cells. The level of internalized Aß within the cells was dependent on the culture time and the kind of apoE isoform present. Both apoE3 and apoE4 enhanced the internalization of Aß; however, no difference was observed between their effects. The internalized Aß was hardly catabolized at all in the presence of apoE4, while rapid clearance of Aß was observed in the presence of apoE3. Unlike apoE3 and apoE4, apoE2 had no effect on Aß clearance from the media. The isoform-specific effects of apoE on the endocytosis of Aß may be implicated in the development of Alzheimer’s disease, and if so, each isoform of apoE would induce a different incidence of that disease.

Keywords: apo E, Alzheimer’s disease, ß-amyloid, senile plaques, flow cytometry, neuroblastoma cells

Abbreviations: apoE, apolipoprotein E; Aß, ß-amyloid; AD, Alzheimer’s disease; CNS, central nervous system; DMSO, dimethyl sulfoxide; PBS, phosphate-buffered saline; ELISA, enzyme-linked immunosorbent assay; FITC, fluorescent isothiocyanate; RAGE, receptor for advanced glycation end-products; LDL, low density lipoprotein; VLDL, very low density lipoprotein




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L. Saavedra, A. Mohamed, V. Ma, S. Kar, and E. P. de Chaves
Internalization of -Amyloid Peptide by Primary Neurons in the Absence of Apolipoprotein E
J. Biol. Chem., December 7, 2007; 282(49): 35722 - 35732.
[Abstract] [Full Text] [PDF]


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