Nature Medicine
2, 224 - 229 (1996)
doi:10.1038/nm0296-224
Alzheimer−associated presenilins 1 and 2 : Neuronal expression in brain and localization to intracellular membranes in mammalian cellsDora M. Kovacs1, Hillary J. Fausett1, Keith J. Page2, Tae-Wan Kim1, Robert D. Moir1, David E. Merriam1, Richard D. Hollister2, Olivia G. Hallmark1, Ronald Mancini1, Kevin M. Felsenstein3, Bradley T. Hyman2, Rudolph E. Tanzi1
& Wilma Wasco1
1Genetics and Aging Unit, and Department of Neurology, Massachusetts General Hospital-East, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
2The Department of Neurology, Massachusetts General Hospital-East, Harvard Medical School, 32 Fruit Street, Boston, Massachusetts 02114, USA
3Bristol Myers-Squibb, 5 Research Parkway, Department 405, Wallingford, Connecticut 06492, USA Correspondence should be addressed to R.E.T. 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.
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