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Presenilin mutations have been hypothesised to cause Alzheimer disease either by altering amyloid precursor protein metabolism or by increasing the vulnerability of neurons to undergo death by apoptosis. We showed previously that PS1 exon 9 deletion (PS1 \u0394E9) and L250S mutations predispose SH\u2010SY5Y neuroblastoma cells to high glucose stress\u2010induced apoptosis and that the anti\u2010apoptotic effect of insulin\u2010like growth factor I (IGF\u2010I) is compromised by these mutations. The present study investigates whether the susceptibility of PS1 mutation transfected SH\u2010SY5Y cells to undergo apoptosis is likely due to a downregulation of Akt\/protein kinase B (Akt), a key intermediate in the phosphatidylinositol 3 (PI3)\u2010kinase arm of the IGF\u2010I signaling pathway. We used two methods to determine the regulation of Akt in response to the pro\u2010apoptotic stimuli of serum deprivation and high glucose stress, as well as treatment with IGF\u2010I. We also looked at the phosphorylatiom state of GSK\u20103\u03b2 at Ser<jats:sup>9<\/jats:sup>. Using a kinase assay with immunoprecipitated Akt, we detected an increased Akt activity in PS1 L250S cells at 1 hr after the combination of 20 mM glucose plus 10 nM IGF\u2010I, when compared to the other cell types. This effect, however, was transient in that no mutation related differences were seen at either 6\u2010 or 24\u2010hr post\u2010treatment. Immunoblotting for Phospho\u2010Akt as a ratio of total Akt, as well as for GSK\u20103\u03b2 phosphorylated at Ser<jats:sup>9<\/jats:sup> revealed no apparent between cell type and treatment differences. This data strongly indicates that PS1 wt and mutant cells show no major differences in the pattern of Akt regulation after exposure to the pro\u2010apoptotic stimuli of either serum deprivation or high glucose stress, or treatment with IGF\u2010I. It is suggested that another component of IGF\u2010I signaling is likely disrupted in these cells to increase their vulnerability to undergo death by apoptosis. J. Neurosci. Res. 66:448\u2013456, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.10006","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:15:54Z","timestamp":1030310154000},"page":"448-456","source":"Crossref","is-referenced-by-count":10,"title":["Akt activity in presenilin 1 wild\u2010type and mutation transfected human SH\u2010SY5Y neuroblastoma cells after serum deprivation and high glucose stress"],"prefix":"10.1002","volume":"66","author":[{"given":"Monika","family":"Vestling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitta","family":"Wiehager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Tanii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard 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