Lack of specific association of presenilin 1 (PS-1) protein with plaques and tangles in Alzheimer's disease.
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.
Alzheimer's Research Unit, Department of Neurology, Massachusetts General Hospital-East, Charlestown 02129, USA.
M Q
MQ
Xia
O
O
Berezovska
T W
TW
Kim
W M
WM
Xia
A
A
Liao
R E
RE
Tanzi
D
D
Selkoe
B T
BT
Hyman
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001254:Astrocytoma / Q000473:pathology; D015153:Blotting, Western; D001923:Brain Chemistry; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005910:Glioma / Q000473:pathology; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis*; D017628:Microglia / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000032:analysis*; D018306:Neurocytoma / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000737:chemistry*; D009474:Neurons / Q000737:chemistry; D058225:Plaque, Amyloid / Q000737:chemistry*; D053764:Presenilin-1; D011993:Recombinant Fusion Proteins / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011993:Recombinant Fusion Proteins