{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T07:06:18Z","timestamp":1779087978974,"version":"3.51.4"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T00:00:00Z","timestamp":1369267200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T00:00:00Z","timestamp":1369267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2013,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To date, no truly effective therapy has been developed for Alzheimer's disease or mild cognitive impairment. In searching for new approaches that may succeed where previous ones have failed, it may be instructive to consider the successful therapeutic developments for other chronic illnesses such as cancer and human immunodeficiency virus.<\/jats:p>","DOI":"10.1002\/emmm.201202307","type":"journal-article","created":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T13:50:16Z","timestamp":1369317016000},"page":"795-798","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Next generation therapeutics for Alzheimer's disease"],"prefix":"10.1038","volume":"5","author":[{"given":"Dale E.","family":"Bredesen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varghese","family":"John","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,5,23]]},"reference":[{"key":"BFEMMM201202307_CR1","doi-asserted-by":"crossref","first-page":"659","DOI":"10.3233\/JAD-2012-121432","volume":"33","author":"C Annweiler","year":"2013","unstructured":"Annweiler C, Llewellyn DJ, Beauchet O (2013) Low serum vitamin D concentrations in Alzheimer's disease: a systematic review and meta\u2010analysis. J Alzheimer's Dis. 33: 659\u2010674","journal-title":"J Alzheimer's Dis."},{"key":"BFEMMM201202307_CR2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1006\/mcne.2001.1030","volume":"18","author":"E Bertrand","year":"2001","unstructured":"Bertrand E, Brouillet E, Caill\u00e9 I, Bouillot C, Cole GM, Prochiantz A, Allinquant B (2001) A short cytoplasmic domain of the amyloid precursor protein induces apoptosis in vitro and in vivo. Mol Cell Neurosci 18: 503\u2010511","journal-title":"Mol Cell Neurosci"},{"key":"BFEMMM201202307_CR3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3233\/JAD-2010-100537","volume":"22","author":"DE Bredesen","year":"2010","unstructured":"Bredesen DE, John V, Galvan V (2010) Importance of the caspase cleavage site in amyloid\u2010\u03b2 protein precursor. J Alzheimer's Dis 22: 57\u201063","journal-title":"J Alzheimer's Dis"},{"key":"BFEMMM201202307_CR4","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.neuron.2011.11.033","volume":"73","author":"A de Calignon","year":"2012","unstructured":"de Calignon A, Polydoro M, Su\u00e1rez\u2010Calvet M, William C, Adamowicz DH, Kopeikina KJ, Pitstick R, Sahara N, Ashe KH, Carlson GA et al (2012) Propagation of tau pathology in a model of early Alzheimer's disease. Neuron 73: 685\u2010697","journal-title":"Neuron"},{"key":"BFEMMM201202307_CR5","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1523\/JNEUROSCI.5433-11.2012","volume":"32","author":"C Deyts","year":"2012","unstructured":"Deyts C, Vetrivel KS, Das S, Shepherd YM, Dupr\u00e9 DJ, Thinakaran G, Parent AT (2012) Novel G\u03b1S\u2010protein signaling associated with membrane\u2010tethered amyloid precursor protein intracellular domain. J Neurosci 32: 1714\u20101729","journal-title":"J Neurosci"},{"key":"BFEMMM201202307_CR6","doi-asserted-by":"crossref","first-page":"8805","DOI":"10.1523\/JNEUROSCI.6159-08.2009","volume":"29","author":"G Dziewczapolski","year":"2009","unstructured":"Dziewczapolski G, Glogowski CM, Masliah E, Heinemann SF (2009) Deletion of the alpha 7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease. J Neurosci 29: 8805\u20108815","journal-title":"J Neurosci"},{"key":"BFEMMM201202307_CR7","doi-asserted-by":"crossref","first-page":"12926","DOI":"10.1073\/pnas.0903200106","volume":"106","author":"YS Eisele","year":"2009","unstructured":"Eisele YS, Bolmont T, Heikenwalder M, Langer F, Jacobson LH, Yan ZX, Roth K, Aguzzi A, Staufenbiel M, Walker LC et al (2009) Induction of cerebral beta\u2010amyloidosis: intracerebral versus systemic Abeta inoculation. Proc Natl Acad Sci USA 106: 12926\u201012931","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201202307_CR8","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1182\/blood.V26.5.642.642","volume":"26","author":"E Frei 3rd","year":"1965","unstructured":"Frei E 3rd, Karon M, Levin RH, Freireich EJ, Taylor RJ, Hananian J, Selawry O, Holland JF, Hoogstraten B, Wolman IJ et al (1965) The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. Blood 26: 642\u2010656","journal-title":"Blood"},{"key":"BFEMMM201202307_CR9","doi-asserted-by":"crossref","first-page":"7130","DOI":"10.1073\/pnas.0509695103","volume":"103","author":"V Galvan","year":"2006","unstructured":"Galvan V, Gorostiza OF, Banwait S, Ataie M, Logvinova AV, Sitaraman S, Carlson E, Sagi SA, Chevallier N, Jin K et al (2006) Reversal of Alzheimer's\u2010like pathology and behavior in human APP transgenic mice by mutation of Asp664. Proc Natl Acad Sci USA 103: 7130\u20107135","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201202307_CR10","doi-asserted-by":"crossref","first-page":"12341","DOI":"10.1074\/jbc.273.20.12341","volume":"273","author":"Q Guo","year":"1998","unstructured":"Guo Q, Robinson N, Mattson MP (1998) Secreted beta\u2010amyloid precursor protein counteracts the proapoptotic action of mutant presenilin\u20101 by activation of NF\u2010kappaB and stabilization of calcium homeostasis. J Biol Chem 273: 12341\u201012351","journal-title":"J Biol Chem"},{"key":"BFEMMM201202307_CR11","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nature11283","volume":"488","author":"T Jonsson","year":"2012","unstructured":"Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, Gudbjartsson D, Maloney J et al (2012) A mutation in APP protects against Alzheimer's disease and age\u2010related cognitive decline. Nature 488: 96\u201099","journal-title":"Nature"},{"key":"BFEMMM201202307_CR12","first-page":"1651","volume":"16","author":"AS Kushwah","year":"2012","unstructured":"Kushwah AS, Singh R, Farswan M, Kaur R (2012) Current therapeutic strategy in Alzheimer's disease. Eur Rev Med Pharm Sci 16: 1651\u20101654","journal-title":"Eur Rev Med Pharm Sci"},{"key":"BFEMMM201202307_CR13","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/74656","volume":"6","author":"DC Lu","year":"2000","unstructured":"Lu DC, Rabizadeh S, Chandra S, Shayya RF, Ellerby LM, Ye X, Salvesen GS, Koo EH, Bredesen DE (2000) A second cytotoxic proteolytic peptide derived from amyloid beta\u2010protein precursor. Nat Med 6: 397\u2010404","journal-title":"Nat Med"},{"key":"BFEMMM201202307_CR14","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1002\/ana.10761","volume":"54","author":"DC Lu","year":"2003","unstructured":"Lu DC, Shaked GM, Masliah E, Bredesen DE, Koo EH (2003) Amyloid beta protein toxicity mediated by the formation of amyloid\u2010beta protein precursor complexes. Ann Neurol 54: 781\u2010789","journal-title":"Ann Neurol"},{"key":"BFEMMM201202307_CR15","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S1474-4422(10)70119-8","volume":"9","author":"F Mangialasche","year":"2010","unstructured":"Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M (2010) Alzheimer's disease: clinical trials and drug development. Lancet 9: 702\u2010716","journal-title":"Lancet"},{"key":"BFEMMM201202307_CR16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3233\/JAD-121735","volume":"34","author":"MT Mizwicki","year":"2013","unstructured":"Mizwicki MT, Liu G, Fiala M, Magpantay L, Sayre J, Siani A, Mahanian M, Weitzman R, Hayden EY, Rosenthal MJ, et al (2013) 1\u03b1,25\u2010dihydroxyvitamin D3 and resolvin D1 retune the balance between amyloid\u2010\u03b2 phagocytosis and ionflammation in Alzheimer's disease patients. J Alzheimer's Dis 34: 155\u2010170","journal-title":"J Alzheimer's Dis"},{"key":"BFEMMM201202307_CR17","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/nature07767","volume":"457","author":"A Nikolaev","year":"2009","unstructured":"Nikolaev A, McLaughlin T, O'Leary DD, Tessier\u2010Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457: 981\u2010989","journal-title":"Nature"},{"key":"BFEMMM201202307_CR18","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2174\/1568007023339166","volume":"1","author":"MJ O'Neill","year":"2002","unstructured":"O'Neill MJ, Murray TK, Lakics V, Visanji NP, Duty S (2002) The role of neuronal nicotinic acetylcholine receptors in acute and chronic neurodegeneration. Curr Drug Targets CNS Neurol Disord 1: 399\u2010411","journal-title":"Curr Drug Targets CNS Neurol Disord"},{"key":"BFEMMM201202307_CR19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12603-011-0012-x","volume":"15","author":"A Piau","year":"2011","unstructured":"Piau A, Nourhash\u00e9mi F, Hein C, Caillaud C, Vellas B (2011) Progress in development of new drugs in Alzheimer's disease. J Nutr Health Aging 15: 45\u201057","journal-title":"J Nutr Health Aging"},{"key":"BFEMMM201202307_CR20","first-page":"S27","volume":"110","author":"P Potter","year":"2010","unstructured":"Potter P (2010) Investigational medications for treatment of patients with Alzheimer's disease. J Am Osteopath Assoc 110: S27\u2010S36","journal-title":"J Am Osteopath Assoc"},{"key":"BFEMMM201202307_CR21","doi-asserted-by":"crossref","first-page":"32549","DOI":"10.1074\/jbc.M110.128439","volume":"285","author":"Y Tian","year":"2010","unstructured":"Tian Y, Crump CJ, Li YM (2010) Dual role of alpha\u2010secretase cleavage in the regulation of gamma\u2010secretase activity for amyloid production. J Biol Chem 285: 32549\u201032556","journal-title":"J Biol Chem"},{"key":"BFEMMM201202307_CR22","doi-asserted-by":"crossref","first-page":"14786","DOI":"10.1074\/jbc.270.24.14786","volume":"270","author":"AJ Yang","year":"1995","unstructured":"Yang AJ, Knauer M, Burdick DA, Glabe C (1995) Intracellular A beta 1\u201042 aggregates stimulate the accumulation of stable, insoluble amyloidogenic fragments of the amyloid precursor protein in transfected cells. J Biol Chem 270: 14786\u201014792","journal-title":"J Biol Chem"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1002\/emmm.201202307.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/emmm.201202307","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1002\/emmm.201202307\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.1002\/emmm.201202307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1002\/emmm.201202307.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:07:23Z","timestamp":1779084443000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1002\/emmm.201202307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,23]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6,1]]}},"alternative-id":["BFEMMM201202307"],"URL":"https:\/\/doi.org\/10.1002\/emmm.201202307","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,23]]},"assertion":[{"value":"23 May 2013","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}