Presenilin-1 protein expression in familial and sporadic Alzheimer's disease
Document Type
Article
Abstract
Mutations of the presenilin PS1 and PS2 genes are closely linked to aggressive forms of early-onset (<60 years) familial Alzheimer's disease. A highly specific monoclonal antibody was developed to identify and characterize the native PS1 protein. Western blot analyses revealed a predominant 32-kd immunoreactive polypeptide in a variety of samples, including PC12 cells transfected with human PS1 complementary DNA, brain biopsy specimens from demented patients, and postmortem samples of frontal neocortex from early-onset familial Alzheimer's disease cases (PS1 and PS2), late-onset sporadic Alzheimer's disease cases, and cases of other degenerative disorders. This truncated polypeptide contains the N-terminus of PS1 and appeared unchanged across cases. In 2 early-onset cases linked to missense mutations in the PS1 gene, a PS1 immunoreactive protein (~49 kd) accumulated in the frontal cortex. This protein was similar in size to full- length PS1 protein present in transfected cells overexpressing PS1 complementary DNA, and in lymphocytes from an affected individual with a deletion of exon 9 of the PS1 gene, suggesting that mutations of the PS1 gene perturb the endoproteolytic processing of the protein. Immunohistochemical studies of control brains revealed that PS1 is expressed primarily in neurons, with the protein localized in the soma and dendritic processes. In contrast, PS1 showed striking localization to the neuropathology in early- onset familial Alzheimer's disease and sporadic Alzheimer's disease cases. PS1 immunoreactivity was present in the neuritic component of senile plaques as well as in neurofibrillary tangles. Localization of PS1 immunoreactivity in familial and sporadic Alzheimer's disease suggests that genetically heterogeneous forms of the disease share a common pathophysiology involving PS1 protein.
Publication Date
6-1-1997
Publication Title
Annals of Neurology
ISSN
03645134
Volume
41
Issue
6
First Page
742
Last Page
753
PubMed ID
9189035
Digital Object Identifier (DOI)
10.1002/ana.410410610
Recommended Citation
Levey, Allan I.; Heilman, Craig J.; Lah, James J.; Nash, Norman R.; Rees, Howard D.; Wakai, Masakazu; Mirra, Suzanne S.; Rye, David B.; Nochlin, David; Bird, Thomas D.; and Mufson, Elliott J., "Presenilin-1 protein expression in familial and sporadic Alzheimer's disease" (1997). Translational Neuroscience. 1919.
https://scholar.barrowneuro.org/neurobiology/1919