TY - JOUR
T1 - Presenilin-1 immunoreactivity is localized intracellularly in Alzheimer's disease brain, but not detected in amyloid plaques
AU - Weber, Libby L.
AU - Leissring, Malcolm A.
AU - Yang, Austin J.
AU - Glabe, Charles G.
AU - Cribbs, David H.
AU - LaFerla, Frank M.
N1 - Funding Information:
This study was supported by National Institutes of Health Grant P50-AGO1542. We thank Ms. Virany Kreng for assistance with the figures and Ms. Andrea Wasserman, Ms. Shari Weinstein, and Mr. Rusty Oshkita of the Irvine Institute for Brain Aging Tissue Repository for the tissue sections used in this study.
PY - 1997/1
Y1 - 1997/1
N2 - The identification of the cellular and subcellular regions of the Alzheimer's disease brain to which the presenilin-1 (PS-1) protein localizes is expected to contribute to an understanding of its pathophysiological role. Toward this end, we have derived an affinity-purified antibody to a synthetic PS-1 peptide. In this report, we demonstrate that this antibody, called SW2, specifically recognizes full-length, 47-kDa PS-1 protein from rat primary cortical neurons, from a human neuronal cell line, and from human brain extracts on Western immunoblots. Immunohistochemical analysis of postmortem brain tissue from control and Alzheimer's disease patients using this SW2 antibody indicates an intracellular localization of PS-1 immunoreactivity with prominent perinuclear characteristics in neurons, with staining also detected in neuritic processes. Despite various treatments of the tissue sections, no PS-1 immunoreactivity was observed in neuritic plaques, the hallmark pathological lesions of Alzheimer's disease. In addition, confocal microscopic analysis of immunostained cultured primary neurons revealed a prominent perinuclear pattern of PS-1 immunoreactivity consistent with vesicular localization, as well as punctate staining in neuritic processes.
AB - The identification of the cellular and subcellular regions of the Alzheimer's disease brain to which the presenilin-1 (PS-1) protein localizes is expected to contribute to an understanding of its pathophysiological role. Toward this end, we have derived an affinity-purified antibody to a synthetic PS-1 peptide. In this report, we demonstrate that this antibody, called SW2, specifically recognizes full-length, 47-kDa PS-1 protein from rat primary cortical neurons, from a human neuronal cell line, and from human brain extracts on Western immunoblots. Immunohistochemical analysis of postmortem brain tissue from control and Alzheimer's disease patients using this SW2 antibody indicates an intracellular localization of PS-1 immunoreactivity with prominent perinuclear characteristics in neurons, with staining also detected in neuritic processes. Despite various treatments of the tissue sections, no PS-1 immunoreactivity was observed in neuritic plaques, the hallmark pathological lesions of Alzheimer's disease. In addition, confocal microscopic analysis of immunostained cultured primary neurons revealed a prominent perinuclear pattern of PS-1 immunoreactivity consistent with vesicular localization, as well as punctate staining in neuritic processes.
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U2 - 10.1006/exnr.1996.6348
DO - 10.1006/exnr.1996.6348
M3 - Article
C2 - 9000444
AN - SCOPUS:0031024228
SN - 0014-4886
VL - 143
SP - 37
EP - 44
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -