The Up‐Regulation of Endosomal‐Lysosomal Components in Amyloid β‐Resistant Cells

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Abstract
: The abundance of amyloid β peptide (Aβ) and the selective loss of neurons are characteristics of Alzheimer's disease. However, subpopulations of brain cells survive, including neurons near Aβ-rich plaques. The surviving neurons may have gene expression profiles that allow them to be resistant to Aβ toxicity. Here we use the differential display technique to compare the profiles of gene expression in an Aβ-resistant cell line with its parental cells. Prominent among the changes are two components of the endosomal-lysosomal system, insulin growth factor II receptor/mannose-6-phosphate receptor and arylsulfatase B. Both are more highly expressed in the Aβ-resistant clone, and arylsulfatase is inducible by Aβ and hydrogen peroxide. Another lysosomal enzyme, βglucuronidase, is also up-regulated in Aβ-resistant cells. These results are consistent with the observation that the endosomal-lysosomal system is highly activated in Alzheimer's disease brains, and they raise the possibility that the high expression of endosomal-lysosomal components is important for neuronal survival in the presence of Aβ.