Abstract
Missense mutations in the presenilin-1 (PS-1) gene are causally related to the majority of familial early-onset Alzheimer's disease (FAD). PS-1 immunohistochemical expression in normal human brain and in brains with Alzheimer's disease (AD) has so far been controversial. Here, we report a study of PS-1 expression in brains, cell lines and peripheral blood mononuclear cells using a panel of well characterized PS-1-specific antibodies. These antibodies were characterized by immunofluorescent staining of PS-1 transfectants followed by flow cytometric analysis. In human brain, widespread neuronal staining was observed. PS-1 immunoreactivity was primarily confined to neuronal cell bodies and proximal dendrites. Weaker staining of microglia was also detected, in accord with the finding of PS-1 immunoreactivity in monocytes. PS-1 expression is not particularly associated with neurons either containing or spared from neurofibrillary tangles, nor with senile plaques. The level of PS-1 expression does not differ between normal and AD brains. Immunoprecipitation from AD, FAD and control brains revealed only a 32 kDa N-terminal fragment and an 18-20 kDa C-terminal fragment. Little or no full length PS-1 was detected. The enriched presence of PS-1 in neurons implies an important role in neuronal function, however, the lack of apparent association of its expression with AD pathology signifies the need for a better understanding of its pathophysiological role.
Original language | English (US) |
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Pages (from-to) | 15-23 |
Number of pages | 9 |
Journal | Journal of the Neurological Sciences |
Volume | 158 |
Issue number | 1 |
DOIs | |
State | Published - Jun 11 1998 |
Keywords
- AD
- Flow cytometry
- Human brain
- Immunohistochemistry
- Immunoprecipitation
- Plaque
- Presenilins
- Tangle
ASJC Scopus subject areas
- Aging
- Clinical Neurology
- Surgery
- Developmental Neuroscience
- Neurology
- Neuroscience(all)