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Volume 16, Number 23, Issue of December 1, 1996 pp. 7513-7525
Copyright ©1996 Society for NeuroscienceExpression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues
Received Aug. 13, 1996; revised Sept. 11, 1996; accepted Sept. 16, 1996.
Michael K. Lee1, 4, Hilda H. Slunt1, 4, Lee J. Martin1, 2, 4, Gopal Thinakaran1, 4, Grace Kim1, 4, Samuel E. Gandy5, Mary Seeger5, Edward Koo6, Donald L. Price1, 2, 3, 4, and Sangram S. Sisodia1, 2, 4 Departments of 1 Pathology, 2 Neuroscience, and 3 Neurology, and the 4 Neuropathology Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, 5 Departments of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, and 6 Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
Mutations in genes encoding related proteins, termed presenilin 1 (PS1) and presenilin 2 (PS2), are linked to the majority of cases with early-onset familial Alzheimer's disease (FAD). To clarify potential function(s) of presenilins and relationships of presenilin expression to pathogenesis of AD, we examined the expression of PS1 and PS2 mRNA and PS1 protein in human and mouse. Semi-quantitative PCR of reverse-transcribed RNA (RT-PCR) analysis revealed that PS1 and PS2 mRNA are expressed ubiquitously and at comparable levels in most human and mouse tissues, including adult brain. However, PS1 mRNA is expressed at significantly higher levels in developing brain. In situ hybridization studies of mouse embryos revealed widespread expression of PS1 mRNA with a neural expression pattern that, in part, overlaps that reported for mRNA encoding specific Notch homologs. In situ hybridization analysis in adult mouse brain revealed that PS1 and PS2 mRNAs are enriched in neurons of the hippocampal formation and entorhinal cortex. Although PS1 and PS2 mRNA are expressed most prominently in neurons, lower but significant levels of PS1 and PS2 transcripts are also detected in white matter glial cells. Moreover, cultured neurons and astrocytes express PS1 and PS2 mRNAs. Using PS1-specific antibodies in immunoblot analysis, we demonstrate that PS1 accumulates as ~28 kDa N-terminal and ~18 kDa C-terminal fragments in brain. Immunocytochemical studies of mouse brain reveal that PS1 protein accumulates in a variety of neuronal populations with enrichment in somatodendritic and neuropil compartments.
Key words: Alzheimer's disease; presenilins; development; mRNA expression; protein accumulation; immunocytochemistry
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