Assessment of normal and mutant human presenilin function in Caenorhabditis elegans

Diane Levitan, Timothy G. Doyle, Denise Brousseau, Michael K. Lee, Gopal Thinakaran, Hilda H. Slunt, Sangram S. Sisodia, Iva Greenwald

Research output: Contribution to journalArticlepeer-review

347 Scopus citations


We provide evidence that normal human presenilins can substitute for Caenorhabditis elegans SEL-12 protein in functional assays in vivo. In addition, six familial Alzheimer disease-linked mutant human presenilins were tested and found to have reduced ability to rescue the sel-12 mutant phenotype, suggesting that they have lower than normal presenilin activity. A human presenilin 1 deletion variant that fails to be proteolytically processed and a mutant SEL-12 protein that lacks the C terminus display considerable activity in this assay, suggesting that neither presenilin proteolysis nor the C terminus is absolutely required for normal presenilin function. We also show that sel-12 is expressed in most neural and nonneural cell types in all developmental stages. The reduced activity of mutant presenilins and as yet unknown gain-of-function properties may be a contributing factor in the development of Alzheimer disease.

Original languageEnglish (US)
Pages (from-to)14940-14944
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - Dec 10 1996


  • Alzheimer disease
  • expression
  • genetics
  • sel-12
  • transgenic nematode


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