{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:25:01Z","timestamp":1791469501302,"version":"4.3.4"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2007,2,1]],"date-time":"2007-02-01T00:00:00Z","timestamp":1170288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2007,2,1]],"date-time":"2007-02-01T00:00:00Z","timestamp":1170288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Rep"],"published-print":{"date-parts":[[2007,2,1]]},"DOI":"10.1038\/sj.embor.7400897","type":"journal-article","created":{"date-parts":[[2007,2,2]],"date-time":"2007-02-02T22:45:23Z","timestamp":1170456323000},"page":"141-146","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":296,"title":["Loss\u2010of\u2010function presenilin mutations in Alzheimer disease"],"prefix":"10.1038","volume":"8","author":[{"given":"Bart","family":"De Strooper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,2,1]]},"reference":[{"key":"BFEMBR7400897_CR1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1006\/nbdi.2001.0473","volume":"9","author":"Z Amtul","year":"2002","unstructured":"Amtul Z et al (2002) A presenilin 1 mutation associated with familial frontotemporal dementia inhibits \u03b3\u2010secretase cleavage of APP and notch. Neurobiol Dis 9: 269\u2013273","journal-title":"Neurobiol Dis"},{"key":"BFEMBR7400897_CR2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev.cellbio.18.020402.142302","volume":"18","author":"W Annaert","year":"2002","unstructured":"Annaert W, De Strooper B (2002) A cell biological perspective on Alzheimer's disease. Annu Rev Cell Dev Biol 18: 25\u201351","journal-title":"Annu Rev Cell Dev Biol"},{"key":"BFEMBR7400897_CR3","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/nature05016","volume":"442","author":"M Baker","year":"2006","unstructured":"Baker M et al (2006) Mutations in progranulin cause tau\u2010negative frontotemporal dementia linked to chromosome 17. Nature 442: 916\u2013919","journal-title":"Nature"},{"key":"BFEMBR7400897_CR4","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1073\/pnas.041603398","volume":"98","author":"L Baki","year":"2001","unstructured":"Baki L et al (2001) Presenilin\u20101 binds cytoplasmic epithelial cadherin, inhibits cadherin\/p120 association, and regulates stability and function of the cadherin\/catenin adhesion complex. Proc Natl Acad Sci USA 98: 2381\u20132386","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR7400897_CR5","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1046\/j.1365-4624.1997.00012.x","volume":"1","author":"R Baumeister","year":"1997","unstructured":"Baumeister R, Leimer U, Zweckbronner I, Jakubek C, Grunberg J, Haass C (1997) Human presenilin\u20101, but not familial Alzheimer's disease (FAD) mutants, facilitate Caenorhabditis elegans Notch signalling independently of proteolytic processing. Genes Funct 1: 149\u2013159","journal-title":"Genes Funct"},{"key":"BFEMBR7400897_CR6","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/j.1471-4159.2005.03578.x","volume":"96","author":"M Bentahir","year":"2006","unstructured":"Bentahir M, Nyabi O, Verhamme J, Tolia A, Horre K, Wiltfang J, Esselmann H, De Strooper B (2006) Presenilin clinical mutations can affect \u03b3\u2010secretase activity by different mechanisms. J Neurochem 96: 732\u2013742","journal-title":"J Neurochem"},{"key":"BFEMBR7400897_CR7","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1093\/brain\/awl268","volume":"129","author":"BF Boeve","year":"2006","unstructured":"Boeve BF et al (2006) Frontotemporal dementia and parkinsonism associated with the IVS1+1G\u2010>A mutation in progranulin: a clinicopathologic study. Brain 129: 3103\u20133114","journal-title":"Brain"},{"key":"BFEMBR7400897_CR8","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0896-6273(00)80230-5","volume":"17","author":"DR Borchelt","year":"1996","unstructured":"Borchelt DR et al (1996) Familial Alzheimer's disease\u2010linked presenilin 1 variants elevate A\u03b21\u201042\/1\u201040 ratio in vitro and in vivo. Neuron 17: 1005\u20131013","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR9","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1111\/j.1471-4159.2006.04091.x","volume":"98","author":"D Chandu","year":"2006","unstructured":"Chandu D, Huppert SS, Kopan R (2006) Analysis of transmembrane domain mutants is consistent with sequential cleavage of Notch by \u03b3\u2010secretase. J Neurochem 98: 2043","journal-title":"J Neurochem"},{"key":"BFEMBR7400897_CR10","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1038\/nature05017","volume":"422","author":"M Cruts","year":"2006","unstructured":"Cruts M et al (2006) Null mutations in progranulin cause ubiquitin\u2010positive frontotemporal dementia linked to chromosome 17q21. Nature 422: 920\u2013924","journal-title":"Nature"},{"key":"BFEMBR7400897_CR11","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0896-6273(00)80998-8","volume":"20","author":"JA Davis","year":"1998","unstructured":"Davis JA, Naruse S, Chen H, Eckman C, Younkin S, Price DL, Borchelt DR, Sisodia SS, Wong PC (1998) An Alzheimer's disease\u2010linked PS1 variant rescues the developmental abnormalities of PS1\u2010deficient embryos. Neuron 20: 603\u2013609","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0896-6273(03)00205-8","volume":"38","author":"B De Strooper","year":"2003","unstructured":"De Strooper B (2003) Aph\u20101, Pen\u20102, and nicastrin with presenilin generate an active \u03b3\u2010secretase complex. Neuron 38: 9\u201312","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR13","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/34910","volume":"391","author":"B De Strooper","year":"1998","unstructured":"De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F (1998) Deficiency of presenilin\u20101 inhibits the normal cleavage of amyloid precursor protein. Nature 391: 387\u2013390","journal-title":"Nature"},{"key":"BFEMBR7400897_CR14","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ana.20083","volume":"55","author":"B Dermaut","year":"2004","unstructured":"Dermaut B et al (2004) A novel presenilin 1 mutation associated with Pick's disease but not \u03b2\u2010amyloid plaques. Ann Neurol 55: 617\u2013626","journal-title":"Ann Neurol"},{"key":"BFEMBR7400897_CR15","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1523\/JNEUROSCI.22-09-03445.2002","volume":"22","author":"I Dewachter","year":"2002","unstructured":"Dewachter I et al (2002) Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long\u2010term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice. J Neurosci 22: 3445\u20133453","journal-title":"J Neurosci"},{"key":"BFEMBR7400897_CR16","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/383710a0","volume":"383","author":"K Duff","year":"1996","unstructured":"Duff K et al (1996) Increased amyloid\u2010\u03b242(43) in brains of mice expressing mutant presenilin 1. Nature 383: 710\u2013713","journal-title":"Nature"},{"key":"BFEMBR7400897_CR17","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0896-6273(01)00523-2","volume":"32","author":"R Feng","year":"2001","unstructured":"Feng R et al (2001) Deficient neurogenesis in forebrain\u2010specific presenilin\u20101 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron 32: 911\u2013926","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR18","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/373523a0","volume":"373","author":"D Games","year":"1995","unstructured":"Games D et al (1995) Alzheimer\u2010type neuropathology in transgenic mice overexpressing V717F \u03b2\u2010amyloid precursor protein. Nature 373: 523\u2013527","journal-title":"Nature"},{"key":"BFEMBR7400897_CR19","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.neurobiolaging.2005.04.017","volume":"27","author":"CG Glabe","year":"2006","unstructured":"Glabe CG (2006) Common mechanisms of amyloid oligomer pathogenesis in degenerative disease. Neurobiol Aging 27: 570\u2013575","journal-title":"Neurobiol Aging"},{"key":"BFEMBR7400897_CR20","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/349704a0","volume":"349","author":"A Goate","year":"1991","unstructured":"Goate A et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349: 704\u2013706","journal-title":"Nature"},{"key":"BFEMBR7400897_CR21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/4789","volume":"5","author":"Q Guo","year":"1999","unstructured":"Guo Q, Fu W, Sopher BL, Miller MW, Ware CB, Martin GM, Mattson MP (1999) Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin\u20101 mutant knock\u2010in mice. Nat Med 5: 101\u2013106","journal-title":"Nat Med"},{"key":"BFEMBR7400897_CR22","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297: 353\u2013356","journal-title":"Science"},{"key":"BFEMBR7400897_CR23","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","volume":"256","author":"JA Hardy","year":"1992","unstructured":"Hardy JA, Higgins GA (1992) Alzheimer's disease: the amyloid cascade hypothesis. Science 256: 184\u2013185","journal-title":"Science"},{"key":"BFEMBR7400897_CR24","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.nbd.2004.08.002","volume":"17","author":"SS H\u00e9bert","year":"2004","unstructured":"H\u00e9bert SS, Serneels L, Dejaegere T, Horr\u00e9 K, Dabrowski M, Baert V, Annaert W, Hartmann D, De Strooper B (2004) Coordinated and widespread expression of \u03b3\u2010secretase in vivo: evidence for size and molecular heterogeneity. Neurobiol Dis 17: 260\u2013272","journal-title":"Neurobiol Dis"},{"key":"BFEMBR7400897_CR25","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/sj.embor.7400704","volume":"7","author":"SS H\u00e9bert","year":"2006","unstructured":"H\u00e9bert SS, Serneels L, Tolia A, Craessaerts K, Derks C, Filippov MA, Muller U, De Strooper B (2006) Regulated intramembrane proteolysis of amyloid precursor protein and regulation of expression of putative target genes. EMBO Rep 7: 739\u2013745","journal-title":"EMBO Rep"},{"key":"BFEMBR7400897_CR26","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/35017105","volume":"2","author":"A Herreman","year":"2000","unstructured":"Herreman A, Serneels L, Annaert W, Collen D, Schoonjans L, De Strooper B (2000) Total inactivation of \u03b3\u2010secretase activity in presenilin\u2010deficient embryonic stem cells. Nat Cell Biol 2: 461\u2013462","journal-title":"Nat Cell Biol"},{"key":"BFEMBR7400897_CR27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0896-6273(94)90458-8","volume":"13","author":"T Iwatsubo","year":"1994","unstructured":"Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y (1994) Visualization of A\u03b242(43) and A\u03b240 in senile plaques with end\u2010specific A\u03b2 monoclonals: evidence that an initially deposited species is A\u03b242(43). Neuron 13: 45\u201353","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR28","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/0092-8674(93)90635-4","volume":"73","author":"JT Jarrett","year":"1993","unstructured":"Jarrett JT, Lansbury PT Jr (1993) Seeding \u201cone\u2010dimensional crystallization\u201d of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? Cell 73: 1055\u20131058","journal-title":"Cell"},{"key":"BFEMBR7400897_CR29","doi-asserted-by":"crossref","first-page":"14776","DOI":"10.1074\/jbc.M513453200","volume":"281","author":"N Kakuda","year":"2006","unstructured":"Kakuda N, Funamoto S, Yagishita S, Takami M, Osawa S, Dohmae N, Ihara Y (2006) Equimolar production of amyloid \u03b2\u2010protein and amyloid precursor protein intracellular domain from \u03b2\u2010carboxyl\u2010terminal fragment by \u03b3\u2010secretase. J Biol Chem 281: 14776\u201314786","journal-title":"J Biol Chem"},{"key":"BFEMBR7400897_CR30","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrm1406","volume":"5","author":"R Kopan","year":"2004","unstructured":"Kopan R, Ilagan MX (2004) \u03b3\u2010secretase: proteasome of the membrane? Nat Rev Mol Cell Biol 5: 499\u2013504","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFEMBR7400897_CR31","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/humu.20336","volume":"27","author":"S Kumar\u2010Singh","year":"2006","unstructured":"Kumar\u2010Singh S, Theuns J, Van Broeck B, Pirici D, Vennekens K, Corsmit E, Cruts M, Dermaut B, Wang R, Van Broeckhoven C (2006) Mean age\u2010of\u2010onset of familial Alzheimer disease caused by presenilin mutations correlates with both increased A\u03b242 and decreased A\u03b240. Hum Mutat 27: 686\u2013695","journal-title":"Hum Mutat"},{"key":"BFEMBR7400897_CR32","doi-asserted-by":"crossref","first-page":"6448","DOI":"10.1073\/pnas.95.11.6448","volume":"95","author":"MP Lambert","year":"1998","unstructured":"Lambert MP et al (1998) Diffusible, nonfibrillar ligands derived from A\u03b21\u201042 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA 95: 6448\u20136453","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR7400897_CR33","doi-asserted-by":"crossref","first-page":"44754","DOI":"10.1074\/jbc.M206872200","volume":"277","author":"S Lammich","year":"2002","unstructured":"Lammich S, Okochi M, Takeda M, Kaether C, Capell A, Zimmer AK, Edbauer D, Walter J, Steiner H, Haass C (2002) Presenilin\u2010dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an A\u03b2\u2010like peptide. J Biol Chem 277: 44754\u201344759","journal-title":"J Biol Chem"},{"key":"BFEMBR7400897_CR34","doi-asserted-by":"crossref","first-page":"6889","DOI":"10.1073\/pnas.0602321103","volume":"103","author":"VK Lazarov","year":"2006","unstructured":"Lazarov VK, Fraering PC, Ye W, Wolfe MS, Selkoe DJ, Li H (2006) Electron microscopic structure of purified, active \u03b3\u2010secretase reveals an aqueous intramembrane chamber and two pores. Proc Natl Acad Sci USA 103: 6889\u20136894","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR7400897_CR35","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nature04533","volume":"440","author":"S Lesne","year":"2006","unstructured":"Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH (2006) A specific amyloid\u2010\u03b2 protein assembly in the brain impairs memory. Nature 440: 352\u2013357","journal-title":"Nature"},{"key":"BFEMBR7400897_CR36","doi-asserted-by":"crossref","first-page":"14940","DOI":"10.1073\/pnas.93.25.14940","volume":"93","author":"D Levitan","year":"1996","unstructured":"Levitan D, Doyle TG, Brousseau D, Lee MK, Thinakaran G, Slunt HH, Sisodia SS, Greenwald I (1996) Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. Proc Natl Acad Sci USA 93: 14940\u201314944","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR7400897_CR37","first-page":"635","volume":"114","author":"P Marambaud","year":"2003","unstructured":"Marambaud P, Wen PH, Dutt A, Shioi J, Takashima A, Siman R, Robakis NK (2003) A CBP binding transcriptional repressor produced by the PS1\/\u03f5\u2010cleavage of N\u2010cadherin is inhibited by PS1 FAD mutations. Cell 114: 635\u2013645","journal-title":"Cell"},{"key":"BFEMBR7400897_CR38","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0896-6273(04)00218-1","volume":"42","author":"E Marjaux","year":"2004","unstructured":"Marjaux E, Hartmann D, De Strooper B (2004) Presenilins in memory, Alzheimer's disease, and therapy. Neuron 42: 189\u2013192","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR39","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.neuron.2005.06.030","volume":"47","author":"E McGowan","year":"2005","unstructured":"McGowan E et al (2005) A\u03b242 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47: 191\u2013199","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR40","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1046\/j.1460-9568.1999.00698.x","volume":"11","author":"Y Nakano","year":"1999","unstructured":"Nakano Y, Kondoh G, Kudo T, Imaizumi K, Kato M, Miyazaki JI, Tohyama M, Takeda J, Takeda M (1999) Accumulation of murine amyloid \u03b242 in a gene\u2010dosage\u2010dependent manner in PS1 \u2018knock\u2010in\u2019 mice. Eur J Neurosci 11: 2577\u20132581","journal-title":"Eur J Neurosci"},{"key":"BFEMBR7400897_CR41","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.1093\/emboj\/cdf541","volume":"21","author":"M Okochi","year":"2002","unstructured":"Okochi M, Steiner H, Fukumori A, Tanii H, Tomita T, Tanaka T, Iwatsubo T, Kudo T, Takeda M, Haass C (2002) Presenilins mediate a dual intramembranous \u03b3\u2010secretase cleavage of Notch\u20101. EMBO J 21: 5408\u20135416","journal-title":"EMBO J"},{"key":"BFEMBR7400897_CR42","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/1531-8249(199903)45:3<358::AID-ANA12>3.0.CO;2-X","volume":"45","author":"JL Price","year":"1999","unstructured":"Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and \u201cpreclinical\u201d Alzheimer's disease. Ann Neurol 45: 358\u2013368","journal-title":"Ann Neurol"},{"key":"BFEMBR7400897_CR43","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1021\/bi0267590","volume":"42","author":"Y Qi","year":"2003","unstructured":"Qi Y, Morishima\u2010Kawashima M, Sato T, Mitsumori R, Ihara Y (2003) Distinct mechanisms by mutant presenilin 1 and 2 leading to increased intracellular levels of amyloid \u03b2\u2010protein 42 in Chinese hamster ovary cells. Biochemistry 42: 1042\u20131052","journal-title":"Biochemistry"},{"key":"BFEMBR7400897_CR44","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0896-6273(00)80999-X","volume":"20","author":"S Qian","year":"1998","unstructured":"Qian S, Jiang P, Guan XM, Singh G, Trumbauer ME, Yu H, Chen HY, Van de Ploeg LH, Zheng H (1998) Mutant human presenilin 1 protects presenilin 1 null mouse against embryonic lethality and elevates A\u03b21\u201042\/43 expression. Neuron 20: 611\u2013617","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR45","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1523\/JNEUROSCI.1575-04.2005","volume":"25","author":"Y Qi\u2010Takahara","year":"2005","unstructured":"Qi\u2010Takahara Y et al (2005) Longer forms of amyloid \u03b2 protein: implications for the mechanism of intramembrane cleavage by \u03b3\u2010secretase. J Neurosci 25: 436\u2013445","journal-title":"J Neurosci"},{"key":"BFEMBR7400897_CR46","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1212\/WNL.55.10.1577","volume":"55","author":"G Raux","year":"2000","unstructured":"Raux G, Gantier R, Thomas\u2010Anterion C, Boulliat J, Verpillat P, Hannequin D, Brice A, Frebourg T, Campion D (2000) Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology 55: 1577\u20131578","journal-title":"Neurology"},{"key":"BFEMBR7400897_CR47","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1016\/j.febslet.2005.04.037","volume":"579","author":"T Sato","year":"2005","unstructured":"Sato T, Tanimura Y, Hirotani N, Saido TC, Morishima\u2010Kawashima M, Ihara Y (2005) Blocking the cleavage at midportion between \u03b3\u2010 and \u03f5\u2010sites remarkably suppresses the generation of amyloid \u03b2\u2010protein. FEBS Lett 579: 2907\u20132912","journal-title":"FEBS Lett"},{"key":"BFEMBR7400897_CR48","doi-asserted-by":"crossref","first-page":"6755","DOI":"10.1523\/JNEUROSCI.1247-05.2005","volume":"25","author":"CA Saura","year":"2005","unstructured":"Saura CA, Chen G, Malkani S, Choi SY, Takahashi RH, Zhang D, Gouras GK, Kirkwood A, Morris RG, Shen J (2005) Conditional inactivation of presenilin 1 prevents amyloid accumulation and temporarily rescues contextual and spatial working memory impairments in amyloid precursor protein transgenic mice. J Neurosci 25: 6755\u20136764","journal-title":"J Neurosci"},{"key":"BFEMBR7400897_CR49","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0896-6273(04)00182-5","volume":"42","author":"CA Saura","year":"2004","unstructured":"Saura CA et al (2004) Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age\u2010dependent neurodegeneration. Neuron 42: 23\u201336","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR50","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/nm0896-864","volume":"2","author":"D Scheuner","year":"1996","unstructured":"Scheuner D et al (1996) Secreted amyloid \u03b2\u2010protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat Med 2: 864\u2013870","journal-title":"Nat Med"},{"key":"BFEMBR7400897_CR51","doi-asserted-by":"crossref","first-page":"13075","DOI":"10.1073\/pnas.1735338100","volume":"100","author":"EH Schroeter","year":"2003","unstructured":"Schroeter EH et al (2003) A presenilin dimer at the core of the \u03b3\u2010secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis. Proc Natl Acad Sci USA 100: 13075\u201313080","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR7400897_CR52","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1073\/pnas.0408901102","volume":"102","author":"L Serneels","year":"2005","unstructured":"Serneels L et al (2005) Differential contribution of the three Aph1 genes to \u03b3\u2010secretase activity in vivo. Proc Natl Acad Sci USA 102: 1719\u20131724","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR7400897_CR53","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.cell.2005.05.022","volume":"122","author":"S Shah","year":"2005","unstructured":"Shah S, Lee SF, Tabuchi K, Hao YH, Yu C, LaPlant Q, Ball H, Dann CE III, Sudhof T, Yu G (2005) Nicastrin functions as a \u03b3\u2010secretase\u2010substrate receptor. Cell 122: 435\u2013447","journal-title":"Cell"},{"key":"BFEMBR7400897_CR54","doi-asserted-by":"crossref","first-page":"41340","DOI":"10.1074\/jbc.M405768200","volume":"279","author":"K Shirotani","year":"2004","unstructured":"Shirotani K, Edbauer D, Prokop S, Haass C, Steiner H (2004) Identification of distinct \u03b3\u2010secretase complexes with different APH\u20101 variants. J Biol Chem 279: 41340\u201341345","journal-title":"J Biol Chem"},{"key":"BFEMBR7400897_CR55","doi-asserted-by":"crossref","first-page":"8717","DOI":"10.1523\/JNEUROSCI.20-23-08717.2000","volume":"20","author":"R Siman","year":"2000","unstructured":"Siman R, Reaume AG, Savage MJ, Trusko S, Lin YG, Scott RW, Flood DG (2000) Presenilin\u20101 P264L knock\u2010in mutation: differential effects on a\u03b2 production, amyloid deposition, and neuronal vulnerability. J Neurosci 20: 8717\u20138726","journal-title":"J Neurosci"},{"key":"BFEMBR7400897_CR56","doi-asserted-by":"crossref","first-page":"6959","DOI":"10.1073\/pnas.96.12.6959","volume":"96","author":"W Song","year":"1999","unstructured":"Song W, Nadeau P, Yuan M, Yang X, Shen J, Yankner BA (1999) Proteolytic release and nuclear translocation of Notch\u20101 are induced by presenilin\u20101 and impaired by pathogenic presenilin\u20101 mutations. Proc Natl Acad Sci USA 96: 6959\u20136963","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR7400897_CR57","doi-asserted-by":"crossref","first-page":"7615","DOI":"10.1074\/jbc.274.12.7615","volume":"274","author":"H Steiner","year":"1999","unstructured":"Steiner H, Romig H, Grim MG, Philipp U, Pesold B, Citron M, Baumeister R, Haass C (1999) The biological and pathological function of the presenilin\u20101 dExon 9 mutation is independent of its defect to undergo proteolytic processing [In Process Citation]. J Biol Chem 274: 7615\u20137618","journal-title":"J Biol Chem"},{"key":"BFEMBR7400897_CR58","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1126\/science.8191290","volume":"264","author":"N Suzuki","year":"1994","unstructured":"Suzuki N, Cheung TT, Cai XD, Odaka A, Otvos L Jr, Eckman C, Golde TE, Younkin SG (1994) An increased percentage of long amyloid \u03b2 protein secreted by familial amyloid \u03b2 protein precursor (\u03b2APP717) mutants. Science 264: 1336\u20131340","journal-title":"Science"},{"key":"BFEMBR7400897_CR59","first-page":"325","volume":"9","author":"J Theuns","year":"2000","unstructured":"Theuns J, Del\u2010Favero J, Dermaut B, van Duijn CM, Backhovens H, Van den Broeck MV, Serneels S, Corsmit E, Van Broeckhoven CV, Cruts M (2000) Genetic variability in the regulatory region of presenilin 1 associated with risk for Alzheimer's disease and variable expression. Hum Mol Genet 9: 325\u2013331","journal-title":"Mol Genet"},{"key":"BFEMBR7400897_CR60","doi-asserted-by":"crossref","first-page":"27633","DOI":"10.1074\/jbc.M604997200","volume":"281","author":"A Tolia","year":"2006","unstructured":"Tolia A, Chavez\u2010Gutierrez L, De Strooper B (2006) Contribution of presenilin transmembrane domains 6 and 7 to a water\u2010containing cavity in the \u03b3\u2010secretase complex. J Biol Chem 281: 27633\u201327642","journal-title":"J Biol Chem"},{"key":"BFEMBR7400897_CR61","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1471-4159.2004.02858.x","volume":"92","author":"ES Walker","year":"2005","unstructured":"Walker ES, Martinez M, Brunkan AL, Goate A (2005) Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in A\u03b2 42\/40 ratios. J Neurochem 92: 294\u2013301","journal-title":"J Neurochem"},{"key":"BFEMBR7400897_CR62","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/416535a","volume":"416","author":"DM Walsh","year":"2002","unstructured":"Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid \u03b2 protein potently inhibit hippocampal long\u2010term potentiation in vivo. Nature 416: 535\u2013539","journal-title":"Nature"},{"key":"BFEMBR7400897_CR63","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.neuroscience.2004.03.048","volume":"126","author":"R Wang","year":"2004","unstructured":"Wang R, Dineley KT, Sweatt JD, Zheng H (2004) Presenilin 1 familial Alzheimer's disease mutation leads to defective associative learning and impaired adult neurogenesis. Neuroscience 126: 305\u2013312","journal-title":"Neuroscience"},{"key":"BFEMBR7400897_CR64","doi-asserted-by":"crossref","first-page":"15330","DOI":"10.1074\/jbc.M512574200","volume":"281","author":"R Wang","year":"2006","unstructured":"Wang R, Wang B, He W, Zheng H (2006) Wild\u2010type presenilin 1 protects against Alzheimer's disease mutation\u2010induced amyloid pathology. J Biol Chem 281: 15330\u201315336","journal-title":"J Biol Chem"},{"key":"BFEMBR7400897_CR65","doi-asserted-by":"crossref","first-page":"31831","DOI":"10.1074\/jbc.M303592200","volume":"278","author":"S Weggen","year":"2003","unstructured":"Weggen S, Eriksen JL, Sagi SA, Pietrzik CU, Ozols V, Fauq A, Golde TE, Koo EH (2003) Evidence that nonsteroidal anti\u2010inflammatory drugs decrease amyloid \u03b2 42 production by direct modulation of \u03b3\u2010secretase activity. J Biol Chem 278: 31831\u201331837","journal-title":"J Biol Chem"},{"key":"BFEMBR7400897_CR66","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1111\/j.1471-4159.2005.03266.x","volume":"94","author":"JC Wiley","year":"2005","unstructured":"Wiley JC, Hudson M, Kanning KC, Schecterson LC, Bothwell M (2005) Familial Alzheimer's disease mutations inhibit \u03b3\u2010secretase\u2010mediated liberation of \u03b2\u2010amyloid precursor protein carboxy\u2010terminal fragment. J Neurochem 94: 1189\u20131201","journal-title":"J Neurochem"},{"key":"BFEMBR7400897_CR67","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.1021\/bi0521846","volume":"45","author":"S Yagishita","year":"2006","unstructured":"Yagishita S, Morishima\u2010Kawashima M, Tanimura Y, Ishiura S, Ihara Y (2006) DAPT\u2010induced intracellular accumulations of longer amyloid \u03b2\u2010proteins: further implications for the mechanism of intramembrane cleavage by \u03b3\u2010secretase. Biochemistry 45: 3952\u20133960","journal-title":"Biochemistry"},{"key":"BFEMBR7400897_CR68","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0896-6273(01)00417-2","volume":"31","author":"H Yu","year":"2001","unstructured":"Yu H et al (2001) APP processing and synaptic plasticity in presenilin\u20101 conditional knockout mice. Neuron 31: 713\u2013726","journal-title":"Neuron"},{"key":"BFEMBR7400897_CR69","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/35017108","volume":"2","author":"Z Zhang","year":"2000","unstructured":"Zhang Z, Nadeau P, Song W, Donoviel D, Yuan M, Bernstein A, Yankner BA (2000) Presenilins are required for \u03b3\u2010secretase cleavage of \u03b2\u2010APP and transmembrane cleavage of Notch\u20101. Nat Cell Biol 2: 463\u2013465","journal-title":"Nat Cell Biol"},{"key":"BFEMBR7400897_CR70","doi-asserted-by":"crossref","first-page":"37689","DOI":"10.1074\/jbc.M507993200","volume":"280","author":"G Zhao","year":"2005","unstructured":"Zhao G, Cui MZ, Mao G, Dong Y, Tan J, Sun L, Xu X (2005) \u03b3\u2010cleavage is dependent on \u03b6\u2010cleavage during the proteolytic processing of amyloid precursor protein within its transmembrane domain. J Biol Chem 280: 37689\u201337697","journal-title":"J Biol Chem"}],"container-title":["The EMBO Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.embor.7400897","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/sj.embor.7400897.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1038\/sj.embor.7400897","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1038\/sj.embor.7400897\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.1038\/sj.embor.7400897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/sj.embor.7400897.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:38:06Z","timestamp":1779136686000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1038\/sj.embor.7400897"}},"subtitle":["Talking Point on the role of presenilin mutations in Alzheimer disease"],"short-title":[],"issued":{"date-parts":[[2007,2,1]]},"references-count":70,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,2,1]]}},"alternative-id":["BFEMBR7400897"],"URL":"https:\/\/doi.org\/10.1038\/sj.embor.7400897","relation":{},"ISSN":["1469-221X","1469-3178"],"issn-type":[{"value":"1469-221X","type":"print"},{"value":"1469-3178","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,2,1]]},"assertion":[{"value":"21 August 2006","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2006","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2007","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}