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<!DOCTYPE html> <html > <head> <meta charset="utf-8"> <meta rel="search" type="application/opensearchdescription+xml" href="/open_search.xml" title="Academia.edu"> <meta content="width=device-width, initial-scale=1" name="viewport"> <meta name="google-site-verification" content="bKJMBZA7E43xhDOopFZkssMMkBRjvYERV-NaN4R6mrs"> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="gSwAxaUu4ApH51zKSMDDMMvD+D/bKxxyho6el8irodihsGDGzUS7yflQ7f/pl3D5GCQ4muYaiyiQr3ks3vdVig==" /> <meta name="citation_title" content="Cell surface expression of the Alzheimer disease-related presenilin proteins" /> <meta name="citation_publication_date" content="1997/01/01" /> <meta name="citation_journal_title" content="Proceedings of the National Academy of Sciences" /> <meta name="citation_author" content="Nazneen Dewji" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:url" content="https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins" /> <meta name="twitter:title" content="Cell surface expression of the Alzheimer disease-related presenilin proteins" /> <meta name="twitter:description" content="The presenilin proteins PS-1 and PS-2 are crucially involved in Alzheimer disease (AD), but their molecular functions are not known. They are integral membrane proteins, but whether they can be expressed at the surface of cells has been in dispute." /> <meta name="twitter:image" content="http://a.academia-assets.com/images/twitter-card.jpeg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins" /> <meta property="og:title" content="Cell surface expression of the Alzheimer disease-related presenilin proteins" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="The presenilin proteins PS-1 and PS-2 are crucially involved in Alzheimer disease (AD), but their molecular functions are not known. They are integral membrane proteins, but whether they can be expressed at the surface of cells has been in dispute." /> <meta property="article:author" content="https://independent.academia.edu/NazneenDewji" /> <meta name="description" content="The presenilin proteins PS-1 and PS-2 are crucially involved in Alzheimer disease (AD), but their molecular functions are not known. They are integral membrane proteins, but whether they can be expressed at the surface of cells has been in dispute." /> <title>(PDF) Cell surface expression of the Alzheimer disease-related presenilin proteins | Nazneen Dewji - Academia.edu</title> <link rel="canonical" href="https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', // Send nil if there is no A/B test bucket, in case some records get logged // with missing data - that way we can distinguish between the two cases. // ab_test_bucket should be of the form <ab_test_name>:<bucket> 'ab_test_bucket': null, }) </script> <script> var $controller_name = 'single_work'; var $action_name = "show"; var $rails_env = 'production'; var $app_rev = '49879c2402910372f4abc62630a427bbe033d190'; var $domain = 'academia.edu'; var $app_host = "academia.edu"; var $asset_host = "academia-assets.com"; var $start_time = new Date().getTime(); var $recaptcha_key = "6LdxlRMTAAAAADnu_zyLhLg0YF9uACwz78shpjJB"; var $recaptcha_invisible_key = "6Lf3KHUUAAAAACggoMpmGJdQDtiyrjVlvGJ6BbAj"; var $disableClientRecordHit = false; </script> <script> window.require = { config: function() { return function() {} } } </script> <script> window.Aedu = window.Aedu || {}; window.Aedu.hit_data = null; window.Aedu.serverRenderTime = new Date(1732468006000); window.Aedu.timeDifference = new Date().getTime() - 1732468006000; </script> <script type="application/ld+json">{"@context":"https://schema.org","@type":"ScholarlyArticle","abstract":"The presenilin proteins PS-1 and PS-2 are crucially involved in Alzheimer disease (AD), but their molecular functions are not known. They are integral membrane proteins, but whether they can be expressed at the surface of cells has been in dispute. Here we show by immunofluorescence experiments, using anti-peptide antibodies specific for either PS-1 or PS-2, that live cultured DAMI cells and differentiated human NT2N neuronal cells are specifically immunolabeled for their endogenous as well as transfected presenilins, although the cells cannot be immunolabeled for their intracellular tubulin, unless they are first fixed and permeabilized. These and other results establish that portions of the presenilins are indeed expressed at the surfaces of these cells. These findings support our previous proposal that the presenilins on the surface of a cell engage in intercellular interactions with the β-amyloid precursor protein on the surface of a neighboring cell, as a critical step in the m...","author":[{"@context":"https://schema.org","@type":"Person","name":"Nazneen Dewji"}],"contributor":[],"dateCreated":"2022-08-06","dateModified":null,"datePublished":"1997-01-01","headline":"Cell surface expression of the Alzheimer disease-related presenilin proteins","inLanguage":"en","keywords":["Membrane Proteins","Multidisciplinary","Antibodies","Cell line","Humans","Neurons","Presenilin-2","Alzheimer Disease","Cell Membrane"],"locationCreated":null,"publication":"Proceedings of the National Academy of Sciences","publisher":{"@context":"https://schema.org","@type":"Organization","name":"Proceedings of the National Academy of Sciences"},"image":null,"thumbnailUrl":null,"url":"https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins","sourceOrganization":[{"@context":"https://schema.org","@type":"EducationalOrganization","name":null}]}</script><link rel="stylesheet" media="all" href="//a.academia-assets.com/assets/single_work_page/loswp-352e32ba4e89304dc0b4fa5b3952eef2198174c54cdb79066bc62e91c68a1a91.css" /><link rel="stylesheet" media="all" href="//a.academia-assets.com/assets/design_system/body-8d679e925718b5e8e4b18e9a4fab37f7eaa99e43386459376559080ac8f2856a.css" /><link rel="stylesheet" media="all" href="//a.academia-assets.com/assets/design_system/button-3cea6e0ad4715ed965c49bfb15dedfc632787b32ff6d8c3a474182b231146ab7.css" /><link rel="stylesheet" media="all" href="//a.academia-assets.com/assets/design_system/text_button-73590134e40cdb49f9abdc8e796cc00dc362693f3f0f6137d6cf9bb78c318ce7.css" /><link crossorigin="" href="https://fonts.gstatic.com/" 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They are integral membrane proteins, but whether they can be expressed at the surface of cells has been in dispute. Here we show by immunofluorescence experiments, using anti-peptide antibodies specific for either PS-1 or PS-2, that live cultured DAMI cells and differentiated human NT2N neuronal cells are specifically immunolabeled for their endogenous as well as transfected presenilins, although the cells cannot be immunolabeled for their intracellular tubulin, unless they are first fixed and permeabilized. These and other results establish that portions of the presenilins are indeed expressed at the surfaces of these cells. These findings support our previous proposal that the presenilins on the surface of a cell engage in intercellular interactions with the β-amyloid precursor protein on the surface of a neighboring cell, as a critical step in the m...","publisher":"Proceedings of the National Academy of Sciences","publication_date":"1997,,","publication_name":"Proceedings of the National Academy of Sciences"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Cell surface expression of the Alzheimer disease-related presenilin proteins","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [35510034]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 'edu.academia.applesignon';</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":89328845,"attachmentType":"pdf"}"><div class="ds-work-cover--blank-cover"><div class="ds-work-cover--blank-cover--title">Cell surface expression of the Alzheimer disease-related presenilin proteins</div></div><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/assets/single_work_splash/adobe.icon-574afd46eb6b03a77a153a647fb47e30546f9215c0ee6a25df597a779717f9ef.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">Cell surface expression of the Alzheimer disease-related presenilin proteins</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="35510034" href="https://independent.academia.edu/NazneenDewji"><img alt="Profile image of Nazneen Dewji" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Nazneen Dewji</a></div><p class="ds-work-card--detail ds2-5-body-sm">1997, Proceedings of the National Academy of Sciences</p><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">The presenilin proteins PS-1 and PS-2 are crucially involved in Alzheimer disease (AD), but their molecular functions are not known. They are integral membrane proteins, but whether they can be expressed at the surface of cells has been in dispute. Here we show by immunofluorescence experiments, using anti-peptide antibodies specific for either PS-1 or PS-2, that live cultured DAMI cells and differentiated human NT2N neuronal cells are specifically immunolabeled for their endogenous as well as transfected presenilins, although the cells cannot be immunolabeled for their intracellular tubulin, unless they are first fixed and permeabilized. These and other results establish that portions of the presenilins are indeed expressed at the surfaces of these cells. These findings support our previous proposal that the presenilins on the surface of a cell engage in intercellular interactions with the β-amyloid precursor protein on the surface of a neighboring cell, as a critical step in the m...</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":89328845,"attachmentType":"pdf","workUrl":"https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":89328845,"attachmentType":"pdf","workUrl":"https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div></div><div data-auto_select="false" data-client_id="331998490334-rsn3chp12mbkiqhl6e7lu2q0mlbu0f1b" data-doc_id="89328845" data-landing_url="https://www.academia.edu/84234636/Cell_surface_expression_of_the_Alzheimer_disease_related_presenilin_proteins" data-login_uri="https://www.academia.edu/registrations/google_one_tap" data-moment_callback="onGoogleOneTapEvent" id="g_id_onload"></div><div class="ds-top-related-works--grid-container"><div class="ds-related-content--container ds-top-related-works--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="0" data-entity-id="28970890" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/28970890/Interaction_between_amyloid_precursor_protein_and_presenilins_in_mammalian_cells_Implications_for_the_pathogenesis_of_Alzheimer_disease">Interaction between amyloid precursor protein and presenilins in mammalian cells: Implications for the pathogenesis of Alzheimer disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="733194" href="https://ttuhsc.academia.edu/RuthPerez">Ruth Perez</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Mutations in the presenilin 1 (PS1) and pre-senilin 2 (PS2) genes increase the production of the highly amyloidogenic 42-residue form of amyloid-protein (A 42) in a variety of cell lines and transgenic mice. To elucidate the molecular mechanism of this effect, wild-type (wt) or mutant PS1 and PS2 genes were stably transfected into Chinese hamster ovary cells expressing endogenous or transfected-amyloid precursor protein (APP). By immunoprecipita-tionWestern blot analysis, APP was consistently found to coimmunoprecipitate with PS1 or PS2 proteins. Several distinct PS1, PS2, or APP antibodies precipitated PS–APP complexes that were detectable by blotting with either APP or PS antibodies. Importantly, complex formation could be detected at endogenous protein levels in nontransfected cells. In various Chinese hamster ovary cell lines, the amounts of APP coprecipitated by PS antibodies were proportional to the expression levels of both APP and PS. APP–PS complexes also were recovered from human 293 and HS683 cells. Full mat-uration of APP was not required for the interaction; most APP molecules complexed with PS were solely N-glycosylated. Treatment of cells with brefeldin A or incubation at 20°C did not block complex formation, suggesting that the association between APP and PS occurs in part in the endoplasmic reticulum. Complex formation was detected for both wt and mutant PS and APP proteins. Deletion of the APP C-terminal domain did not abrogate complex formation, suggesting that the interaction does not occur in the cytoplasmic domains of the proteins. Our results demonstrate that wt and mutant PS1 and PS2 proteins form complexes with APP in living cells, strongly supporting the hypothesis that mutant PS interacts with APP in a way that enhances the intramembranous proteolysis of the latter by a-secretase cleaving at A 42 .</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Interaction between amyloid precursor protein and presenilins in mammalian cells: Implications for the pathogenesis of Alzheimer disease","attachmentId":49412176,"attachmentType":"pdf","work_url":"https://www.academia.edu/28970890/Interaction_between_amyloid_precursor_protein_and_presenilins_in_mammalian_cells_Implications_for_the_pathogenesis_of_Alzheimer_disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/28970890/Interaction_between_amyloid_precursor_protein_and_presenilins_in_mammalian_cells_Implications_for_the_pathogenesis_of_Alzheimer_disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="17391762" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/17391762/Neuronal_localization_of_presenilin_1_and_association_with_amyloid_plaques_and_neurofibrillary_tangles_in_Alzheimers_disease">Neuronal localization of presenilin-1 and association with amyloid plaques and neurofibrillary tangles in Alzheimer's disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="37118796" href="https://boehringer-ingelheim.academia.edu/BerndSommer">Bernd Sommer</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The Journal of neuroscience : the official journal of the Society for Neuroscience, 1997</p><p class="ds-related-work--abstract ds2-5-body-sm">Mutations in the presenilin-1 (PS1) gene is a cause of early- onset familial Alzheimer&#39;s disease (AD). Endogenous PS1 is associated with the endoplasmic reticulum in the cell body of undifferentiated SH-SY5Y neuroblastoma cells. At early stages of neuronal differentiation in rat hippocampal culture, PS1 appears in all neuritic processes and in growth cones. In mature differentiated neurons, PS1 is concentrated in the somatodendritic compartment but is also present at lower levels in axons. A similar localization of PS1 is observed in vivo in neurons of the adult human cerebral cortex. In sporadic AD, PS1 appears in the dystrophic neurites of mature amyloid plaques and co-localizes with a subset of intraneuronal neurofibrillary tangles (NFTs). About 30% of hippocampal NFTs are labeled with a highly specific antibody to the PS1 C-terminal loop domain but not with an antibody to the PS1 N terminus. 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data-collection-position="4" data-entity-id="24893951" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/24893951/Proteolytic_Fragments_of_Alzheimer_s_Disease_Associated_Presenilin_1_Are_Present_in_Synaptic_Organelles_and_Growth_Cone_Membranes_of_Rat_Brain">Proteolytic Fragments of Alzheimer’s Disease-Associated Presenilin 1 Are Present in Synaptic Organelles and Growth Cone Membranes of Rat Brain</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39659278" href="https://independent.academia.edu/ColinMasters">Colin Masters</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Neurochemistry, 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Proteolytic 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class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="23569397" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/23569397/The_Role_of_Alzheimers_Disease_Related_Presenilin_1_in_Intercellular_Adhesion">The Role of Alzheimer's Disease-Related Presenilin 1 in Intercellular Adhesion</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="45602722" href="https://independent.academia.edu/MVitek">Michael Vitek</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Experimental Cell Research, 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The Role of Alzheimer's Disease-Related Presenilin 1 in Intercellular Adhesion","attachmentId":43993901,"attachmentType":"pdf","work_url":"https://www.academia.edu/23569397/The_Role_of_Alzheimers_Disease_Related_Presenilin_1_in_Intercellular_Adhesion","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/23569397/The_Role_of_Alzheimers_Disease_Related_Presenilin_1_in_Intercellular_Adhesion"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="17226694" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/17226694/Immunohistochemical_analysis_of_presenilin_2_expression_in_the_mouse_brain_distribution_pattern_and_co_localization_with_presenilin_1_protein">Immunohistochemical analysis of presenilin 2 expression in the mouse brain: distribution pattern and co-localization with presenilin 1 protein</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="36835689" href="https://independent.academia.edu/LaurentPradier">Laurent Pradier</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Brain Research, 1997</p><p class="ds-related-work--abstract ds2-5-body-sm">Missense mutations of presenilin 1 (PS-1) and presenilin 2 (PS-2) genes cause the majority of early-onset familial forms of Alzheimer&amp;#39;s disease (AD). We previously characterized the distribution of the PS-1 protein in the mouse brain by immunohistochemistry using an antibody directed against an epitope located in the large hydrophilic loop [Moussaoui, S., Czech, C., Pradier, L., Blanchard, V., Bonici, B., Gohin, M., Imperato, A. and Revah, F., Immunohistochemical analysis of presenilin 1 expression in the mouse brain, FEBS Lett., 383 (1996) 219-222]. Similarly, we now report the distribution pattern of PS-2 protein in the mouse brain. For these experiments we used a polyclonal antibody raised against a synthetic peptide corresponding to the amino-acid sequence 7-24 of the predicted human PS-2 protein. The specificity of the antibody was evidenced by its ability to recognize PS-2 protein in immunoprecipitation studies and by antigen-peptide competition. In the mouse brain, PS-2 protein was present in numerous cerebral structures, but its distribution in these structures did not correlate with their susceptibility to AD pathology. In all examined structures of the gray matter, PS-2 protein was concentrated in neuronal cell bodies but it was not detected in the glial cells of the white matter. The regional distribution pattern of PS-2 protein was almost identical to that of PS-1 protein. Moreover, PS-2 protein co-localized with PS-1 protein in a large number of neuronal cell bodies. In terms of subcellular localization, PS-2 immunostaining was present almost exclusively in neuronal cell bodies while PS-1 immunostaining was also present in dendrites. This could be explained by the different epitopes of the antibodies and the known proteolytic processing of both presenilins in vivo [Tanzi, R.E., Kovacs, D.M., Kim, T.-W., Moir, R.D., Guenette, S.Y. and Wasco, W., The presenilin genes and their role in early-onset familial Alzheimer&amp;#39;s disease, Alzheimer&amp;#39;s disease Rev., 1 (1996) 91-98]. Within neuronal cell bodies, the immunostaining of PS-2 protein, as well as that of PS-1 protein, had a reticular and granular appearance. This suggests in agreement with previous observations on PS-1 and PS-2 in COS and H4 cells [Kovacs, D.M., Fausett, H.J., Page, K.J., Kim, T.-W., Moir, R.D., Merriam, D.E., Hollister, R.D., Hallmark, O.G., Mancini, R., Felsenstein, K.M., Hyman, B.T., Tanzi, R.E., Wasco, W., Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells, Nature Med., 2 (1996) 224-229] that these proteins are situated in intracytoplasmic organelles, possibly the endoplasmic reticulum and the Golgi complex.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Immunohistochemical analysis of presenilin 2 expression in the mouse brain: distribution pattern and co-localization with presenilin 1 protein","attachmentId":42290252,"attachmentType":"pdf","work_url":"https://www.academia.edu/17226694/Immunohistochemical_analysis_of_presenilin_2_expression_in_the_mouse_brain_distribution_pattern_and_co_localization_with_presenilin_1_protein","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/17226694/Immunohistochemical_analysis_of_presenilin_2_expression_in_the_mouse_brain_distribution_pattern_and_co_localization_with_presenilin_1_protein"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="22086630" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/22086630/Identification_of_neuronal_plasma_membrane_microdomains_that_colocalize_beta_amyloid_and_presenilin_implications_for_beta_amyloid_precursor_protein_processing">Identification of neuronal plasma membrane microdomains that colocalize beta-amyloid and presenilin: implications for beta-amyloid precursor protein processing</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="43384584" href="https://uio.academia.edu/ReidunTorp">Reidun Torp</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neuroscience, 2003</p><p class="ds-related-work--abstract ds2-5-body-sm">Alzheimer&#39;s disease (AD) is associated with the accumulation of extracellular deposits of the beta-amyloid protein (Abeta). Abeta is a result of misprocessing of the beta-amyloid precursor protein (APP). Gamma-secretase is involved in APP misprocessing and one hypothesis holds that this secretase is identical to PS1. We tested this hypothesis by determining whether PS is co-localised with Abeta in situ. Using confocal analyses and a sensitive immunogold procedure we show that PS and Abeta are co-localised within discrete microdomains of neuronal plasma membranes in AD patients and in aged dogs, an established model of human brain aging. Our data indicate that APP misprocessing occurs in discrete plasma membrane domains of neurons and provide evidence that PS1 is critically involved in Abeta formation.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Identification of neuronal plasma membrane microdomains that colocalize beta-amyloid and presenilin: implications for beta-amyloid precursor protein processing","attachmentId":42759891,"attachmentType":"pdf","work_url":"https://www.academia.edu/22086630/Identification_of_neuronal_plasma_membrane_microdomains_that_colocalize_beta_amyloid_and_presenilin_implications_for_beta_amyloid_precursor_protein_processing","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/22086630/Identification_of_neuronal_plasma_membrane_microdomains_that_colocalize_beta_amyloid_and_presenilin_implications_for_beta_amyloid_precursor_protein_processing"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="64646253" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/64646253/Lack_of_specific_association_of_presenilin_1_PS_1_protein_with_plaques_and_tangles_in_Alzheimers_disease">Lack of specific association of presenilin 1 (PS-1) protein with plaques and tangles in Alzheimer's disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="103612531" href="https://harvard.academia.edu/RudyTanzi">Rudy Tanzi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of the Neurological Sciences, 1998</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Lack of specific association of presenilin 1 (PS-1) protein with plaques and tangles in Alzheimer's disease","attachmentId":76585144,"attachmentType":"pdf","work_url":"https://www.academia.edu/64646253/Lack_of_specific_association_of_presenilin_1_PS_1_protein_with_plaques_and_tangles_in_Alzheimers_disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/64646253/Lack_of_specific_association_of_presenilin_1_PS_1_protein_with_plaques_and_tangles_in_Alzheimers_disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="50922444" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/50922444/Immunoreactivity_of_Presenilin_1_and_Tau_in_Alzheimers_Disease_Brain">Immunoreactivity of Presenilin-1 and Tau in Alzheimer's Disease Brain</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32274528" href="https://independent.academia.edu/ChristineVanBroeckhoven">Christine Van Broeckhoven</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Experimental Neurology, 1998</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Immunoreactivity of Presenilin-1 and Tau in Alzheimer's Disease Brain","attachmentId":68798585,"attachmentType":"pdf","work_url":"https://www.academia.edu/50922444/Immunoreactivity_of_Presenilin_1_and_Tau_in_Alzheimers_Disease_Brain","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/50922444/Immunoreactivity_of_Presenilin_1_and_Tau_in_Alzheimers_Disease_Brain"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" 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data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Amyloid precursor protein and presenilin 1 interaction studied by FRET in human H4 cells","attachmentId":50532653,"attachmentType":"pdf","work_url":"https://www.academia.edu/2938763/Amyloid_precursor_protein_and_presenilin_1_interaction_studied_by_FRET_in_human_H4_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/2938763/Amyloid_precursor_protein_and_presenilin_1_interaction_studied_by_FRET_in_human_H4_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="6" data-entity-id="59971412" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/59971412/A_family_of_membrane_proteins_associated_with_presenilin_expression_and_secretase_function">A family of membrane proteins associated with presenilin expression and -secretase function</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33151542" href="https://independent.academia.edu/TakeshiTabira">Takeshi Tabira</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The FASEB Journal, 2007</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A family of membrane proteins associated with presenilin expression and -secretase 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ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/116185749/Presenilin_1_protein_expression_in_familial_and_sporadic_Alzheimers_disease">Presenilin‐1 protein expression in familial and sporadic Alzheimer's disease</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="53381990" href="https://independent.academia.edu/ThomasBird6">Thomas Bird</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Annals of Neurology, 1997</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Presenilin‐1 protein expression in familial and sporadic Alzheimer's disease","attachmentId":112386330,"attachmentType":"pdf","work_url":"https://www.academia.edu/116185749/Presenilin_1_protein_expression_in_familial_and_sporadic_Alzheimers_disease","alternativeTracking":true}"><span 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class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="50662016" href="https://independent.academia.edu/hvanderstichele">hugo vanderstichele</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Nature, 1998</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein","attachmentId":74843309,"attachmentType":"pdf","work_url":"https://www.academia.edu/61938490/Deficiency_of_presenilin_1_inhibits_the_normal_cleavage_of_amyloid_precursor_protein","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline 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class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33473615" href="https://utoronto.academia.edu/HowardMount">Howard Mount</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biological Chemistry, 2000</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Carboxyl-terminal Fragments of Alzheimer β-Amyloid Precursor Protein Accumulate in Restricted and Unpredicted Intracellular Compartments in Presenilin 1-deficient Cells","attachmentId":89403159,"attachmentType":"pdf","work_url":"https://www.academia.edu/84348977/Carboxyl_terminal_Fragments_of_Alzheimer_%CE%B2_Amyloid_Precursor_Protein_Accumulate_in_Restricted_and_Unpredicted_Intracellular_Compartments_in_Presenilin_1_deficient_Cells","alternativeTracking":true}"><span class="material-symbols-outlined" 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href="https://www.academia.edu/77877220/Widespread_immunoreactivity_of_presenilin_in_neurons_of_normal_and_Alzheimers_disease_brains_double_labeling_immunohistochemical_study">Widespread immunoreactivity of presenilin in neurons of normal and Alzheimer's disease brains: double-labeling immunohistochemical study</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38561576" href="https://sorbonne-fr.academia.edu/KhalidHachimi">Khalid Hachimi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Acta Neuropathologica, 1996</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Widespread immunoreactivity of presenilin in neurons of normal and Alzheimer's disease brains: double-labeling immunohistochemical 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data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26809894/Presenilin_1_immunoreactive_neurons_are_preserved_in_late_onset_Alzheimers_disease">Presenilin-1-immunoreactive neurons are preserved in late-onset Alzheimer's disease</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="3271495" href="https://mssm.academia.edu/JunichiShioi">Junichi Shioi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The American journal of pathology, 1997</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Presenilin-1-immunoreactive neurons are preserved in late-onset Alzheimer's 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ds2-5-body-link" href="https://www.academia.edu/114533538/Brain_Expression_of_Presenilins_in_Sporadic_and_Early_onset_Familial_Alzheimer_s_Disease">Brain Expression of Presenilins in Sporadic and Early-onset, Familial Alzheimer’s Disease</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="112502703" href="https://independent.academia.edu/PaulFraser12">Paul Fraser</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular Medicine, 2000</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Brain Expression of Presenilins in Sporadic and Early-onset, Familial Alzheimer’s Disease","attachmentId":111207360,"attachmentType":"pdf","work_url":"https://www.academia.edu/114533538/Brain_Expression_of_Presenilins_in_Sporadic_and_Early_onset_Familial_Alzheimer_s_Disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/114533538/Brain_Expression_of_Presenilins_in_Sporadic_and_Early_onset_Familial_Alzheimer_s_Disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="13" data-entity-id="115768677" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/115768677/Intraneuronal_APP_A%CE%B2_Trafficking_and_Plaque_Formation_in_%CE%B2_Amyloid_Precursor_Protein_and_Presenilin_1_Transgenic_Mice">Intraneuronal APP/Aβ Trafficking and Plaque Formation in β-Amyloid Precursor Protein and Presenilin-1 Transgenic Mice</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="293467928" href="https://independent.academia.edu/veroniqueBlanchard1">veronique Blanchard</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Brain Pathology, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Intraneuronal APP/Aβ Trafficking and Plaque Formation in β-Amyloid Precursor Protein and Presenilin-1 Transgenic Mice","attachmentId":112082650,"attachmentType":"pdf","work_url":"https://www.academia.edu/115768677/Intraneuronal_APP_A%CE%B2_Trafficking_and_Plaque_Formation_in_%CE%B2_Amyloid_Precursor_Protein_and_Presenilin_1_Transgenic_Mice","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/115768677/Intraneuronal_APP_A%CE%B2_Trafficking_and_Plaque_Formation_in_%CE%B2_Amyloid_Precursor_Protein_and_Presenilin_1_Transgenic_Mice"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="14" data-entity-id="84234637" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/84234637/The_presenilins_turned_inside_out_Implications_for_their_structures_and_functions">The presenilins turned inside out: Implications for their structures and functions</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35510034" href="https://independent.academia.edu/NazneenDewji">Nazneen Dewji</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Proceedings of the National Academy of Sciences, 2004</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The presenilins turned inside out: Implications for their structures and functions","attachmentId":89328841,"attachmentType":"pdf","work_url":"https://www.academia.edu/84234637/The_presenilins_turned_inside_out_Implications_for_their_structures_and_functions","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/84234637/The_presenilins_turned_inside_out_Implications_for_their_structures_and_functions"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="15" data-entity-id="30529691" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/30529691/Alzheimer_s_disease_presenilin_1_expression_modulates_the_assembly_of_neurofilaments">Alzheimer’s disease presenilin-1 expression modulates the assembly of neurofilaments</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="58189284" href="https://independent.academia.edu/WieslawDowjat">Wieslaw Dowjat</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neuroscience, 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Alzheimer’s disease presenilin-1 expression modulates the assembly of neurofilaments","attachmentId":50972891,"attachmentType":"pdf","work_url":"https://www.academia.edu/30529691/Alzheimer_s_disease_presenilin_1_expression_modulates_the_assembly_of_neurofilaments","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/30529691/Alzheimer_s_disease_presenilin_1_expression_modulates_the_assembly_of_neurofilaments"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="16" data-entity-id="56310980" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/56310980/Proteolytic_Fragments_of_the_Alzheimers_Disease_Associated_Presenilins_1_and_2_Are_Phosphorylated_in_Vivo_by_Distinct_Cellular_Mechanisms_">Proteolytic Fragments of the Alzheimer's Disease Associated Presenilins-1 and -2 Are Phosphorylated in Vivo by Distinct Cellular Mechanisms †</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="40718159" href="https://independent.academia.edu/MartinCitron">Martin Citron</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochemistry, 1998</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Proteolytic Fragments of the Alzheimer's Disease Associated Presenilins-1 and -2 Are Phosphorylated in Vivo by Distinct Cellular Mechanisms †","attachmentId":71759854,"attachmentType":"pdf","work_url":"https://www.academia.edu/56310980/Proteolytic_Fragments_of_the_Alzheimers_Disease_Associated_Presenilins_1_and_2_Are_Phosphorylated_in_Vivo_by_Distinct_Cellular_Mechanisms_","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/56310980/Proteolytic_Fragments_of_the_Alzheimers_Disease_Associated_Presenilins_1_and_2_Are_Phosphorylated_in_Vivo_by_Distinct_Cellular_Mechanisms_"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="17" data-entity-id="27840803" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/27840803/Are_Presenilins_Intramembrane_Cleaving_Proteases_Implications_for_the_Molecular_Mechanism_of_Alzheimers_Disease_">Are Presenilins Intramembrane-Cleaving Proteases? Implications for the Molecular Mechanism of Alzheimer's Disease †</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="52176645" href="https://hms-harvard.academia.edu/MichaelWolfe">Michael Wolfe</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochemistry, 1999</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Are Presenilins Intramembrane-Cleaving Proteases? 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