The up-regulation of endosomal-lysosomal components in amyloid beta-resistant cells

The abundance of amyloid beta peptide (A beta) and the selective loss of ne urons are characteristics of Alzheimer's disease. However, subpopulations o f brain cells survive, including neurons near A beta-rich plaques. The surv iving neurons may have gene expression profiles that allow them to be resis tant to A beta toxicity. Here we use the differential display technique to compare the profiles of gene expression in an A beta-resistant cell line wi th its parental cells. Prominent among the changes are two components of th e endosomal-lysosomal system, insulin growth factor II receptor/mannose-6-p hosphate receptor and arylsulfatase B. Both are more highly expressed in th e A beta-resistant clone, and arylsulfatase is inducible by A beta and hydr ogen peroxide. Another lysosomal enzyme, beta-glucuronidase, is also up-reg ulated in A beta-resistant cells. These results are consistent with the obs ervation that the endosomal-lysosomal system is highly activated in Alzheim er's disease brains, and they raise the possibility that the high expressio n of endosomal-lysosomal components is important for neuronal survival in t he presence of A beta.