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• W2000895856 abstract "Aggregation of the neurotoxic amyloid β peptide 1-42 (Aβ-(1-42)) in the brain is considered to be an early event in the pathogenesis of Alzheimer's disease (AD). Par-4 (prostate apoptosis response-4) is a leucine zipper protein that is pro-apoptotic and associated with neuronal degeneration in AD. Overexpression of Par-4 significantly increased production of Aβ-(1-42) after initiation of apoptotic cascades, indicating factors regulating apoptotic pathways may also affect processing of β-amyloid precursor protein (APP). AATF (apoptosis-antagonizing transcription factor) was recently identified as an interaction partner of DAP-like kinase (Dlk), a member of the DAP (death-associated protein) kinase family. AATF antagonizes apoptosis induced by Par-4, suggesting that AATF might directly or indirectly participate in regulation of Par-4 activity. We now report that AATF colocalizes with Par-4 in both cytoplasmic and nuclear compartments, and it interacts directly and selectively with Par-4 via the leucine zipper domain in neural cells. Par-4 induced an aberrant production and secretion of Aβ in neuroblastoma IMR-32 cells after apoptotic cascades are initiated. Co-expression of AATF completely blocked aberrant production and secretion of Aβ-(1-42) induced by Par-4, and AATF/Par-4 complex formation was essential for the inhibitory effect of AATF on aberrant Aβ secretion. These results indicate that AATF is an endogenous antagonist of Par-4 activity and an effective inhibitor of aberrant Aβ production and secretion under apoptotic conditions. Aggregation of the neurotoxic amyloid β peptide 1-42 (Aβ-(1-42)) in the brain is considered to be an early event in the pathogenesis of Alzheimer's disease (AD). Par-4 (prostate apoptosis response-4) is a leucine zipper protein that is pro-apoptotic and associated with neuronal degeneration in AD. Overexpression of Par-4 significantly increased production of Aβ-(1-42) after initiation of apoptotic cascades, indicating factors regulating apoptotic pathways may also affect processing of β-amyloid precursor protein (APP). AATF (apoptosis-antagonizing transcription factor) was recently identified as an interaction partner of DAP-like kinase (Dlk), a member of the DAP (death-associated protein) kinase family. AATF antagonizes apoptosis induced by Par-4, suggesting that AATF might directly or indirectly participate in regulation of Par-4 activity. We now report that AATF colocalizes with Par-4 in both cytoplasmic and nuclear compartments, and it interacts directly and selectively with Par-4 via the leucine zipper domain in neural cells. Par-4 induced an aberrant production and secretion of Aβ in neuroblastoma IMR-32 cells after apoptotic cascades are initiated. Co-expression of AATF completely blocked aberrant production and secretion of Aβ-(1-42) induced by Par-4, and AATF/Par-4 complex formation was essential for the inhibitory effect of AATF on aberrant Aβ secretion. These results indicate that AATF is an endogenous antagonist of Par-4 activity and an effective inhibitor of aberrant Aβ production and secretion under apoptotic conditions. It is widely accepted that neuronal degeneration in Alzheimer's disease (AD) 1The abbreviations used are: ADAlzheimer's diseaseAATFapoptosis-antagonizing transcription factorPar-4prostate apoptosis response-4Leu.zipleucine zipper domainAβamyloid β peptideAPPβ-amyloid precursor proteinELISAenzyme-linked immunosorbent assayPS-1presenilin-1PBSphosphate-buffered salineANOVAanalysis of variance. may be caused by extracellular accumulation of aggregated, neurotoxic amyloid β peptide 1-42 (Aβ-(1-42), Refs. 1Selkoe D.J. Science. 2002; 298: 789-791Crossref PubMed Scopus (3446) Google Scholar, 2Hardy J. Selkoe D.J. Science. 2002; 297: 353-356Crossref PubMed Scopus (11137) Google Scholar, 3Esler W.P. Wolfe M.S. Science. 2001; 293: 1449-1454Crossref PubMed Scopus (474) Google Scholar, 4Haass C. De Strooper B. Science. 1999; 286: 916-919Crossref PubMed Scopus (368) Google Scholar, 5Price D.L. Sisodia S.S. Borchelt D.R. 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The leucine zipper domain of Par-4 mediates protein-protein interactions, and is essential for pro-apoptotic actions of Par-4 in neuronal cells (46Guo Q. Fu W. Xie J. Luo H. Sells S.F. Geddes J.W. Bondada V. Rangnekar V.M. Mattson M.P. Nat. Med. 1998; 4: 957-962Crossref PubMed Scopus (254) Google Scholar). Overexpression of Par-4 in neuroblastoma IMR-32 cells significantly increased production of Aβ-(1-42) through a caspase-dependent pathway (40Guo Q. Xie J. Chang X. Du H. J..Biol. Chem. 2001; 276: 16040-16044Abstract Full Text Full Text PDF Scopus (24) Google Scholar). These results suggest that Par-4 is involved in the abnormal processing of APP during the apoptotic process. Alzheimer's disease apoptosis-antagonizing transcription factor prostate apoptosis response-4 leucine zipper domain amyloid β peptide β-amyloid precursor protein enzyme-linked immunosorbent assay presenilin-1 phosphate-buffered saline analysis of variance. AATF (apoptosis-antagonizing transcription factor) was recently identified as an interaction partner of DAP-like kinase (Dlk), a member of the DAP (death-associated protein) kinase family of pro-apoptotic serine/threonine kinases (50Page G. Lodige I. Kogel D. Scheidtmann K.H. FEBS Lett. 1999; 462: 187-191Crossref PubMed Scopus (76) Google Scholar, 51Kogel D. Bierbaum H. Preuss U. Scheidtmann K.H. Oncogene. 1999; 18: 7212-7218Crossref PubMed Scopus (42) Google Scholar, 52Kogel D. Prehn J.H. Scheidtmann K.H. Bioessays. 2001; 23: 352-358Crossref PubMed Scopus (88) Google Scholar, 53Shohat G. Shani G. Eisenstein M. Kimchi A. Biochim. Biophys. Acta. 2002; 1600: 45-50Crossref PubMed Scopus (63) Google Scholar, 54Engemann H. Heinzel V. Page G. Preuss U. Scheidtmann K.H. Nucleic Acids Res. 2002; 30: 1408-1417Crossref PubMed Scopus (19) Google Scholar, 55Kogel D. Reimertz C. Dussmann H. Mech P. Scheidtmann K.H. Prehn J.H. Eur. J. Cancer. 2003; 39: 249-256Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 56Kogel D. Reimertz C. Mech P. Poppe M. Fruhwald M.C. Engemann H. Scheidtmann K.H. Prehn J.H. Br. J. Cancer. 2001; 85: 1801-1808Crossref PubMed Scopus (53) Google Scholar, 57Lindfors K. Halttunen T. Huotari P. Nupponen N. Vihinen M. Visakorpi T. Maki M. Kainulainen H. Biochem. Biophys. Res. Commun. 2000; 276: 660-666Crossref PubMed Scopus (37) Google Scholar, 58Page G. Kogel D. Rangnekar V. Scheidtmann K.H. Oncogene. 1999; 18: 7265-7273Crossref PubMed Scopus (96) Google Scholar). AATF contains a putative leucine zipper domain and several putative phosphorylation sites for protein kinases CKII, cAMP-dependent protein kinase, and protein kinase C (50Page G. Lodige I. Kogel D. Scheidtmann K.H. FEBS Lett. 1999; 462: 187-191Crossref PubMed Scopus (76) Google Scholar, 51Kogel D. Bierbaum H. Preuss U. Scheidtmann K.H. Oncogene. 1999; 18: 7212-7218Crossref PubMed Scopus (42) Google Scholar, 52Kogel D. Prehn J.H. Scheidtmann K.H. Bioessays. 2001; 23: 352-358Crossref PubMed Scopus (88) Google Scholar, 53Shohat G. Shani G. Eisenstein M. Kimchi A. Biochim. Biophys. Acta. 2002; 1600: 45-50Crossref PubMed Scopus (63) Google Scholar, 54Engemann H. Heinzel V. Page G. Preuss U. Scheidtmann K.H. Nucleic Acids Res. 2002; 30: 1408-1417Crossref PubMed Scopus (19) Google Scholar, 55Kogel D. Reimertz C. Dussmann H. Mech P. Scheidtmann K.H. Prehn J.H. Eur. J. Cancer. 2003; 39: 249-256Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 56Kogel D. Reimertz C. Mech P. Poppe M. Fruhwald M.C. Engemann H. Scheidtmann K.H. Prehn J.H. Br. J. Cancer. 2001; 85: 1801-1808Crossref PubMed Scopus (53) Google Scholar, 57Lindfors K. Halttunen T. Huotari P. Nupponen N. Vihinen M. Visakorpi T. Maki M. Kainulainen H. Biochem. Biophys. Res. Commun. 2000; 276: 660-666Crossref PubMed Scopus (37) Google Scholar, 58Page G. Kogel D. Rangnekar V. Scheidtmann K.H. Oncogene. 1999; 18: 7265-7273Crossref PubMed Scopus (96) Google Scholar). Human AATF has an open reading frame of 560 amino acids and contains several potential phosphorylation sites, a leucine zipper structure, putative nuclear localization signals (NLS1 and NLS2), and three nuclear receptor-binding motifs. Importantly, AATF antagonizes apoptosis induced by Par-4 (50Page G. Lodige I. Kogel D. Scheidtmann K.H. FEBS Lett. 1999; 462: 187-191Crossref PubMed Scopus (76) Google Scholar, 51Kogel D. Bierbaum H. Preuss U. Scheidtmann K.H. Oncogene. 1999; 18: 7212-7218Crossref PubMed Scopus (42) Google Scholar, 52Kogel D. Prehn J.H. Scheidtmann K.H. Bioessays. 2001; 23: 352-358Crossref PubMed Scopus (88) Google Scholar, 53Shohat G. Shani G. Eisenstein M. Kimchi A. Biochim. Biophys. Acta. 2002; 1600: 45-50Crossref PubMed Scopus (63) Google Scholar, 54Engemann H. Heinzel V. Page G. Preuss U. Scheidtmann K.H. Nucleic Acids Res. 2002; 30: 1408-1417Crossref PubMed Scopus (19) Google Scholar, 55Kogel D. Reimertz C. Dussmann H. Mech P. Scheidtmann K.H. Prehn J.H. Eur. J. Cancer. 2003; 39: 249-256Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 56Kogel D. Reimertz C. Mech P. Poppe M. Fruhwald M.C. Engemann H. Scheidtmann K.H. Prehn J.H. Br. J. Cancer. 2001; 85: 1801-1808Crossref PubMed Scopus (53) Google Scholar, 57Lindfors K. Halttunen T. Huotari P. Nupponen N. Vihinen M. Visakorpi T. Maki M. Kainulainen H. Biochem. Biophys. Res. Commun. 2000; 276: 660-666Crossref PubMed Scopus (37) Google Scholar, 58Page G. Kogel D. Rangnekar V. Scheidtmann K.H. Oncogene. 1999; 18: 7265-7273Crossref PubMed Scopus (96) Google Scholar), suggesting that AATF might participate in inhibition of pro-apoptotic and/or activation of anti-apoptotic pathways. We now report that AATF interacts directly with Par-4 via the leucine zipper domain, and blocks Par-4 mediated aberrant production of Aβ-(1-42) in IMR-32 cells. Our data suggest that AATF may function as an endogenous inhibitor of Par-4 activity in APP processing. Selective enhancement of AATF expression in neuronal cells may therefore provide a potential therapeutic approach for aberrant production of Aβ-(1-42) in AD. Hippocampal Neuronal Cultures—Dissociated hippocampal cell cultures were prepared from postnatal day 1 mouse pups using methods similar to those described previously (47Guo Q. Fu W. Sopher B.L. Miller M.W. Ware C.B. Martin G.M. Mattson M.P. Nat. Med. 1999; 5: 101-106Crossref PubMed Scopus (410) Google Scholar). Briefly, hippocampi were removed and incubated for 15 min in Ca2+- and Mg2+-free Hank's balanced saline solution (Invitrogen Life Technologies, Inc.) containing 0.2% papain. Cells were dissociated by trituration and plated into polyethyleneimine-coated plastic or glass-bottom culture dishes containing minimum essential medium with Earle's salts supplemented with 10% heat-inactivated fetal bovine serum, 2 mml-glutamine, 1 mm pyruvate, 20 mm KCl, 10 mm sodium bicarbonate, and 1 mm Hepes (pH 7.2). Following cell attachment (3-6-h post-plating), the culture medium was replaced with Neurobasal Medium with B27 supplements (Invitrogen, Life Technologies, Inc.). Experiments were performed in 7-day-old cultures. Generation and Characterization of IMR-32 Cell Lines and Trophic Factor Withdrawal—Methods used in transfection experiments and induction of apoptosis by trophic factor withdrawal were described in our previous studies (40Guo Q. Xie J. Chang X. Du H. J..Biol. Chem. 2001; 276: 16040-16044Abstract Full Text Full Text PDF Scopus (24) Google Scholar, 41Guo Q. Xie J. Du H. Brain Res. 2000; 874: 221-232Crossref PubMed Scopus (11) Google Scholar, 46Guo Q. Fu W. Xie J. Luo H. Sells S.F. Geddes J.W. Bondada V. Rangnekar V.M. Mattson M.P. Nat. Med. 1998; 4: 957-962Crossref PubMed Scopus (254) Google Scholar, 47Guo Q. Fu W. Sopher B.L. Miller M.W. Ware C.B. Martin G.M. Mattson M.P. Nat. Med. 1999; 5: 101-106Crossref PubMed Scopus (410) Google Scholar, 48Guo Q. Sebastian L. Sopher B.L. Miller M.W. Glazner G.W. Ware C.B. Martin G.M. Mattson M.P. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 4125-4130Crossref PubMed Scopus (121) Google Scholar). In brief, human neuroblastoma IMR-32 cells (ATCC) were maintained at 37 °C in an atmosphere of 95% air and 5% CO2 in Eagle's minimum essential medium supplemented with non-essential amino acids, and 10% heat-inactivated fetal bovine serum. A full-length Par-4 cDNA was subcloned into the expression vector pRc/CMV, yielding a recombinant construct pCMV-Par-4, which encodes a 1.2-kb RNA species and a full-length 38kD Par-4 protein. A cDNA fragment containing Par-4 lacking the leucine zipper domain (Par-4ΔLeu.zip) was similarly subcloned into pRc/CMV expression vector, yielding a recombinant construct pCMV-Par4ΔLeuzip that encodes an 862-bp RNA species and an ∼30-kDa protein. A cDNA fragment containing full-length wild-type AATF and cDNAs containing various deletion mutants of AATF (see Ref. 50Page G. Lodige I. Kogel D. Scheidtmann K.H. FEBS Lett. 1999; 462: 187-191Crossref PubMed Scopus (76) Google Scholar), including AATF 390 (deletion of the C terminus NLS2), AATF 279 (deletion of the C terminus NLS2 and NSL1), AATF 179 (deletion of the C terminus NLS2, NSL1 and the putative leucine zipper domain), were subcloned into the pREP4 expression vector (Invitrogen), yielding recombinant constructs pREP4-AATF, pREP4-AATF390, pREP4-AATF279, and pREP4-AATF179. Human IMR-32 cell lines stably expressing Par-4 or Par4ΔLeuzip were established by transfection using LipofectAMINE (Invitrogen/Life Technologies, Inc.) with pCMV-Par-4 or pCMV-Par4ΔLeuzip. Transfected cells were selected with G418 (400 μg/ml) for 4 weeks, and surviving clones were selected. IMR-32 cells expressing AATF, AATF 390, AATF 279, and AATF 179 were similarly established except that the transfected cells were selected with hygromycin (400 μg/ml). Additional double-transfected IMR-32 cell lines were generated where two proteins (Par-4/AATF, Par4ΔLeuzip/AATF, Par-4/AATF390, Par-4/AATF279, or Par-4/AATF179) were co-expressed. For control purposes, parallel cultures of IMR-32 cells were stably transfected with pRc/CMV and pREP4 vectors alone. After the cells became confluent in the culture flasks, the culture medium were replaced with fresh media and incubated for 48 h at 37 °C to condition the medium for Aβ measurement. Trophic factor withdrawal was initiated by washing cultures four times with Locke's buffer (154 mm NaCl, 5.6 mm KCl, 2.3 mm CaCl2, 1.0 mm MgCl2, 3.6 mm NaHCO3, 5 mm glucose, and 5 mm HEPES, pH 7.2) with subsequent incubation in 1 ml of Locke's buffer. Generation of AATF Antibody, Immunoprecipitation, and Western Blot Analysis—Levels of expression of Par-4 and AATF in hippocampal neurons were determined by Western blot analysis as described (46Guo Q. Fu W. Xie J. Luo H. Sells S.F. Geddes J.W. Bondada V. Rangnekar V.M. Mattson M.P. Nat. Med. 1998; 4: 957-962Crossref PubMed Scopus (254) Google Scholar, 47Guo Q. Fu W. Sopher B.L. Miller M.W. Ware C.B. Martin G.M. Mattson M.P. Nat. Med. 1999; 5: 101-106Crossref PubMed Scopus (410) Google Scholar, 48Guo Q. Sebastian L. Sopher B.L. Miller M.W. Glazner G.W. Ware C.B. Martin G.M. Mattson M.P. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 4125-4130Crossref PubMed Scopus (121) Google Scholar). A suitable peptide sequence (LDTDKRYSGKTTSRKAWKE, corresponding to rat AATF terminus amino acids 64-82) from AATF was chosen based on its antigenicity and other considerations. The BLAST program was used to compare the peptide sequence against known sequences in the major databases to avoid similarity and cross-reactivity with other related and unrelated proteins. The peptide was conjugated to the carrier protein keyhole limpet hemocyanin (KLH) and used to immunize rabbits to generate AATF antisera (Sigma-Genosys, The Woodlands, TX) according to standard protocols. Crude antisera were affinity-purified further by adsorption of antibodies to the peptide that had been immobilized to Sepharose. Purified antibodies were eluted with ImmunoPure Gentle Ag/Ab elution buffer. The antibody was finally dialyzed, concentrated, and used at a dilution of 1:100 in Western blots. The specificity of the AATF antisera was analyzed by passing it down affinity columns containing the immobilized peptide and analyzing both the unbound fractions and eluted fractions in Western blots. We have found that the antibody recognizes rat, mouse and human AATF on Western blots. It revealed a strong band at about 70 kDa in whole cell protein extracts from both human IMR-32 cells and mouse primary neurons. The antibody recognizes AATF390, AATF 279, and AATF 179 as well as full-length AATF. The Par-4 antibody is a mouse monoclonal antibody raised against full-length rat Par-4 (Santa Cruz Biotechnology, Inc). This antibody reacts with Par-4 of mouse, rat, and human origin, and recognizes both full-length Par-4 as well as the deletion mutant of Par-4 (Par-4ΔLeu.zip) that lacks the leucine zipper domain. In addition, the antibody recognizes both human and rodent Par-4 proteins at about 38 kDa. For immunoprecipitation, aliquots of cell lysates containing 200 μg of protein were incubated for 1 h at 4 °C with appropriate dilutions of mouse anti-Par-4 or rabbit anti-AATF antibodies in immunoprecipitation buffer (150 mm NaCl, 2 mm EDTA, 1% Nonidet P-40, 5 μg/ml leupeptin, 5 μg/ml aprotinin, 2 μg/ml pepstatin A, 0.25 mm phenylmethylsulfonyl fluoride, 50 mm Tris, pH 7.6). Protein A-Sepharose resin (Amersham Biosciences, 30 μl/sample) was then added to the extracts for collection of the immunocomplexes, which was then washed three times in immunoprecipitation buffer, and solubilized by heating in Laemmli buffer containing 2-mercaptoethanol at 100 °C for 4 min. The solubilized proteins were separated by electro-phoresis on a 4-12% gradient SDS-polyacrylamide gel and then transferred to a nitrocellulose sheet. For Western blot analysis, the nitrocellulose sheet was blocked with 5% milk followed by a 1-h incubation in the presence of primary anti-AATF or anti-Par4 antibody. The membrane was further processed using horseradish peroxidase-conjugated secondary antibody and immunoblotted proteins were detected by chemiluminescence using the ECL system (Amersham Biosciences). To examine if AATF or Par-4 interacts with c-Jun, a leucine zipper containing transcription factor of about 39 kDa, a mouse monoclonal anti-c-Jun antibody (Oncogene Research Products, San Diego, CA) was used in the immunoprecipitation/Western blot analysis. Equal loading was verified by probing the blots with the anti-tubulin antibody (Sigma). Western blot images were acquired and quantified using Kodak Image Station 2000R and Kodak Digital Science 1D 3.6. software. Immunocytochemistry by Confocal Laser Scanning Microscopy—The cultured cells were fixed for 30 min in 4% paraformaldehyde/PBS, and membranes were permeabilized by incubation in 0.2% Triton-X100 in PBS. Cells were incubated for 1 h in blocking serum (5% normal goat serum in PBS). Cells were then exposed to primary antibodies (1:100 dilution of rabbit anti-AATF polyclonal antibody and 1:100 mouse anti-Par-4 monoclonal antibody) overnight at 4 °C, followed by incubation for 1 h with a mixture of Texas Red-labeled anti-rabbit and fluorescein-labeled anti-mouse secondary antibodies (Vector Laboratories, Burlingame, CA). Images of Par-4 and/or AATF immunofluorescence were acquired using a confocal laser-scanning microscope (dual wave-length scan) with a ×60 oil immersion objective. All images were acquired using the same laser intensity and photodector gain, to allow quantitative comparisons of relative levels of fluorescence in the cells. The average pixel intensity per cell and sites of colocalization of immunoreactivities were determined using the Fluoview 2.0 software. Preparation of Whole Cell, Cytosolic, Membrane, and Nuclear Extracts—After washing 3 times with cold PBS, whole cell extracts were prepared in lysis buffer as described in our previous studies (37Guo Q. Xie J. Chang X. Zhang X. Du H. Brain Res. 2001; 903: 13-25Crossref PubMed Scopus (14) Google Scholar, 46Guo Q. Fu W. Xie J. Luo H. Sells S.F. Geddes J.W. Bondada V. Rangnekar V.M. Mattson M.P. Nat. Med. 1998; 4: 957-962Crossref PubMed Scopus (254) Google Scholar). Nuclear, cytosolic and membrane fractions from IMR-32 human neuroblastoma cells were isolated as described previously (59Chatterjee T.K. Fisher R.A. J. Biol. Chem. 2000; 275: 24013-24021Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar), with some modifications. Briefly, cells were washed with cold PBS and homogenized in a tight-fitting Dounce homogenizer in cold lysis buffer containing 5 mm Tris-HCl, pH 7.4, 1 mm EGTA, 1 mm EDTA, 2 mm MgCl2, 10 mm KCl, 1 mm dithiothreitol, 1 mm 4-(2-aminoethyl) benzenesulfonyl fluoride, 1 μm leupeptin, 1 μm aprotinin, 1 μm pepstatin, 1 μm bestatin, and 1 μm E64. 0.5 ml of the cell lysate was then layered onto a solution of 1.1 m sucrose in lysis buffer (0.5 ml) and centrifuged at 1500 × g for 10 min at 4 °C. The supernatant from this step contains cytosolic as well as membrane fractions, while the pellet contains nuclear extract. The supernatant was further centrifuged at 15,000 × g for 30 min at 4 °C. The resulting supernatant and pellet were cytosolic and membrane fractions, respectively. The nuclear pellet was washed by resuspension in 1 ml of 1.1 m sucrose in lysis buffer and recentrifugation at 1500 × g for 5 min at 4 °C. The identity of these fractions has been confirmed previously by immunoblotting studies using various specific organelle markers (59Chatterjee T.K. Fisher R.A. J. Biol. Chem. 2000; 275: 24013-24021Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar). Quantification of Extracellular and Intracellular Levels of Aβ-(1-40) and Aβ-(1-42) by Sandwich ELISAs—Aβ-(1-40) and Aβ-(1-42) levels in the conditioned culture media were measured using a fluorescence-based sandwich ELISA described in detail in our previous studies (40Guo Q. Xie J. Chang X. Du H. J..Biol. Chem. 2001; 276: 16040-16044Abstract Full Text Full Text PDF Scopus (24) Google Scholar). The C-terminal-specific sandwich ELISAs use a monoclonal antibody directed against the N-terminal region of human Aβ and two other antibodies specific for Aβ-(1-40) and Aβ-(1-42) (see Ref. 40Guo Q. Xie J. Chang X. Du H. J..Biol. Chem. 2001; 276: 16040-16044Abstract Full Text Full Text PDF Scopus (24) Google Scholar). The ratio (%) of" @default.
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• W2000895856 title "AATF Inhibits Aberrant Production of Amyloid β Peptide 1-42 by Interacting Directly with Par-4" @default.
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