Alzheimer-associated presenilins 1 and 2: Neuronal expression in brain and localization to intracellular membranes in mammalian cells

Dora M. Kovacs, Hillary J. Fausett, Keith J. Page, Tae Wan Kim, Robert D. Moir, David E. Merriam, Richard D. Hollister, Olivia G. Hallmark', Ronald Mancini, Kevin M. Felsenstein, Bradley T. Hyman, Rudolph E. Tanzi, Wilma Wasco

Research output: Contribution to journalArticle

497 Scopus citations

Abstract

Mutations in two recently identified genes appear to cause the majority of early-onset familial Alzheimer's disease (FAD). These two novel genes, presenilin 1 (PS1) and presenilin 2 (PS2) are members of an evolutionarily conserved gene family. The normal biological role(s) of the presenilins and the mechanism(s) by which the FAD-associated mutations exert their effect remain unknown. Employing in situ hybridization, we demonstrate that the expression patterns of PS1 and PS2 in the brain are extremely similar to each other and that messages for both are primarily detectable in neuronal populations. Immunochemical analyses indicate that PS1 and PS2 are similar in size and localized to similar intracellular compartments (endoplasmic reticulum and Golgi complex). FAD-associated mutations in PS1 and PS2 do not significantly modify either their migration patterns on SDS-polyacrylamide gel electrophoresis or their overall subcellular localization, although subtle differences in perinuclear staining were noted for mutant PS1.

Original languageEnglish (US)
Pages (from-to)224-229
Number of pages6
JournalNature medicine
Volume2
Issue number2
DOIs
StatePublished - Feb 16 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Alzheimer-associated presenilins 1 and 2: Neuronal expression in brain and localization to intracellular membranes in mammalian cells'. Together they form a unique fingerprint.

  • Cite this

    Kovacs, D. M., Fausett, H. J., Page, K. J., Kim, T. W., Moir, R. D., Merriam, D. E., Hollister, R. D., Hallmark', O. G., Mancini, R., Felsenstein, K. M., Hyman, B. T., Tanzi, R. E., & Wasco, W. (1996). Alzheimer-associated presenilins 1 and 2: Neuronal expression in brain and localization to intracellular membranes in mammalian cells. Nature medicine, 2(2), 224-229. https://doi.org/10.1038/nm0296-224