{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:51:06Z","timestamp":1780545066195,"version":"3.54.1"},"reference-count":174,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2016,5,23]],"date-time":"2016-05-23T00:00:00Z","timestamp":1463961600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2016,5,23]]},"DOI":"10.3233\/jad-151186","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T12:02:02Z","timestamp":1464091322000},"page":"781-799","source":"Crossref","is-referenced-by-count":48,"title":["Evidence For and Against a Pathogenic Role of Reduced \u03b3-Secretase Activity in Familial Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"52","author":[{"given":"Tanya","family":"Jayne","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Disease Genetics Laboratory, Centre for Molecular Pathology, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Newman","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Genetics Laboratory, Centre for Molecular Pathology, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Verdile","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Curtin Health Innovation Research Institute \u2013 Biosciences, Faculty of Health Sciences, Curtin University, Kent Street, Bentley, WA, Australia"},{"name":"School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia"},{"name":"McCusker Alzheimer\u2019s Disease Research Foundation, Hollywood Private Hospital, Hollywood Medical Centre, Nedlands, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Discipline of Pathology, Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"M\u00fcnch","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Group & School of Medicine, Western Sydney University, Campbelltown NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Musgrave","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology, School of Medicine, University of Adelaide, North Terrace, Adelaide, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyyed Hani","family":"Moussavi Nik","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Genetics Laboratory, Centre for Molecular Pathology, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lardelli","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Genetics Laboratory, Centre for Molecular Pathology, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-151186_ref1","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/S0140-6736(96)10203-8","article-title":"Auguste D and Alzheimer\u2019s disease","volume":"349","author":"Maurer","year":"1997","journal-title":"Lancet"},{"key":"10.3233\/JAD-151186_ref2","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/0006-291X(84)91209-9","article-title":"Alzheimer\u2019s disease and Down\u2019s syndrome: Sharing of a unique cerebrovascular amyloid fibril protein","volume":"122","author":"Glenner","year":"1984","journal-title":"Biochem Biophys Res Commun"},{"key":"10.3233\/JAD-151186_ref3","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S0006-291X(84)80190-4","article-title":"Alzheimer\u2019s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein","volume":"120","author":"Glenner","year":"1984","journal-title":"Biochem Biophys Res Commun"},{"key":"10.3233\/JAD-151186_ref4","doi-asserted-by":"crossref","first-page":"8729","DOI":"10.1073\/pnas.82.24.8729","article-title":"Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related","volume":"82","author":"Wong","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-151186_ref5","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","article-title":"Amyloid plaque core protein in Alzheimer disease and Down syndrome","volume":"82","author":"Masters","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-151186_ref6","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/349704a0","article-title":"Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer\u2019s disease","volume":"349","author":"Goate","year":"1991","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref7","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/375754a0","article-title":"Cloning of a gene bearing missense mutations in early-onset familial Alzheimer\u2019s disease","volume":"375","author":"Sherrington","year":"1995","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref8","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1126\/science.7638622","article-title":"Candidate gene for the chromosome 1 familial Alzheimer\u2019s disease locus","volume":"269","author":"Levy-Lahad","year":"1995","journal-title":"Science"},{"key":"10.3233\/JAD-151186_ref9","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/nm0896-864","article-title":"Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer\u2019s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer\u2019s disease","volume":"2","author":"Scheuner","year":"1996","journal-title":"Nat Med"},{"key":"10.3233\/JAD-151186_ref10","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/383710a0","article-title":"Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1","volume":"383","author":"Duff","year":"1996","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref11","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0896-6273(00)80230-5","article-title":"Familial Alzheimer\u2019s disease-linked presenilin 1 variants elevate Abeta1-42\/1-40 ratio in vitro and in vivo","volume":"17","author":"Borchelt","year":"1996","journal-title":"Neuron"},{"key":"10.3233\/JAD-151186_ref12","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/35017105","article-title":"Total inactivation of gamma-secretase activity in presenilin-deficient embryonic stem cells","volume":"2","author":"Herreman","year":"2000","journal-title":"Nat Cell Biol"},{"key":"10.3233\/JAD-151186_ref13","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/ejhg.2011.225","article-title":"A genome-wide study reveals rare CNVs exclusive to extreme phenotypes of Alzheimer disease","volume":"20","author":"Rovelet-Lecrux","year":"2012","journal-title":"Eur J Hum Genet"},{"key":"10.3233\/JAD-151186_ref14","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/mp.2012.15","article-title":"High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease","volume":"17","author":"Pottier","year":"2012","journal-title":"Mol Psychiatry"},{"key":"10.3233\/JAD-151186_ref15","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/34910","article-title":"Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein","volume":"391","author":"De Strooper","year":"1998","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref16","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/19077","article-title":"Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity","volume":"398","author":"Wolfe","year":"1999","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref17","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/ncb960","article-title":"Reconstitution of gamma-secretase activity","volume":"5","author":"Edbauer","year":"2003","journal-title":"Nat Cell Biol"},{"key":"10.3233\/JAD-151186_ref18","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1073\/pnas.0608332104","article-title":"The presenilin hypothesis of Alzheimer\u2019s disease: Evidence for a loss-of-function pathogenic mechanism","volume":"104","author":"Shen","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-151186_ref19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/sj.embor.7400897","article-title":"Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease","volume":"8","author":"De Strooper","year":"2007","journal-title":"EMBO Rep"},{"key":"10.3233\/JAD-151186_ref20","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/0092-8674(93)90635-4","article-title":"Seeding one-dimensional crystallization of amyloid: A pathogenic mechanism in Alzheimer\u2019s disease and scrapie?","volume":"73","author":"Jarrett","year":"1993","journal-title":"Cell"},{"key":"10.3233\/JAD-151186_ref21","doi-asserted-by":"crossref","first-page":"7053","DOI":"10.1523\/JNEUROSCI.17-18-07053.1997","article-title":"Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse","volume":"17","author":"Irizarry","year":"1997","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-151186_ref22","doi-asserted-by":"crossref","first-page":"a006338","DOI":"10.1101\/cshperspect.a006338","article-title":"Neurotoxicity of amyloid beta-protein: Synaptic and network dysfunction","volume":"2","author":"Mucke","year":"2012","journal-title":"Cold Spring Harb Perspect Med"},{"key":"10.3233\/JAD-151186_ref23","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/nrd3505","article-title":"The amyloid cascade hypothesis for Alzheimer\u2019s disease: An appraisal for the development of therapeutics","volume":"10","author":"Karran","year":"2011","journal-title":"Nat Rev Drug Discov"},{"key":"10.3233\/JAD-151186_ref24","doi-asserted-by":"crossref","unstructured":"(2010) Why are drug trials in Alzheimer\u2019s disease failing? Lancet 376, 658.","DOI":"10.1016\/S0140-6736(10)61316-5"},{"key":"10.3233\/JAD-151186_ref25","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nn.4017","article-title":"The case for rejecting the amyloid cascade hypothesis","volume":"18","author":"Herrup","year":"2015","journal-title":"Nat Neurosci"},{"key":"10.3233\/JAD-151186_ref26","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/nn.4018","article-title":"Three dimensions of the amyloid hypothesis: Time, space and wingmen","volume":"18","author":"Musiek","year":"2015","journal-title":"Nat Neurosci"},{"key":"10.3233\/JAD-151186_ref27","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3233\/JAD-2010-1221","article-title":"Alzheimer\u2019s disease and the amyloid-beta peptide","volume":"19","author":"Murphy","year":"2010","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-151186_ref28","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S1097-2765(00)00061-7","article-title":"Requirements for presenilin-dependent cleavage of notch and other transmembrane proteins","volume":"6","author":"Struhl","year":"2000","journal-title":"Mol Cell"},{"key":"10.3233\/JAD-151186_ref29","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1038\/ncb1101-1030","article-title":"Endogenous beta-amyloid production in presenilin-deficient embryonic mouse fibroblasts","volume":"3","author":"Armogida","year":"2001","journal-title":"Nat Cell Biol"},{"key":"10.3233\/JAD-151186_ref30","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/nn898","article-title":"Presenilins are not required for A beta 42 production in the early secretory pathway","volume":"5","author":"Wilson","year":"2002","journal-title":"Nat Neurosci"},{"key":"10.3233\/JAD-151186_ref31","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.1073\/pnas.052017699","article-title":"Notch receptor cleavage depends on but is not directly executed by presenilins","volume":"99","author":"Taniguchi","year":"2002","journal-title":"Proc Natl Acad SciU S A"},{"key":"10.3233\/JAD-151186_ref32","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1471-4159.2005.03528.x","article-title":"A presenilin-independent aspartyl protease prefers the gamma-42 site cleavage","volume":"96","author":"Lai","year":"2006","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-151186_ref33","doi-asserted-by":"crossref","first-page":"14958","DOI":"10.1021\/bi981063l","article-title":"Processing of the Alzheimer\u2019s disease amyloid precursor protein in Pichia pastoris: Immunodetection of alpha-, beta-, and gamma-secretase products","volume":"37","author":"Le Brocque","year":"1998","journal-title":"Biochemistry"},{"key":"10.3233\/JAD-151186_ref34","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/35015085","article-title":"Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1","volume":"405","author":"Li","year":"2000","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref35","doi-asserted-by":"crossref","first-page":"21435","DOI":"10.1073\/pnas.1013246107","article-title":"Activation and intrinsic gamma-secretase activity of presenilin 1","volume":"107","author":"Ahn","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-151186_ref36","doi-asserted-by":"crossref","first-page":"14185","DOI":"10.1021\/bi00043a024","article-title":"Candidate gamma-secretases in the generation of the carboxyl terminus of the Alzheimer\u2019s disease beta A4 amyloid: Possible involvement of cathepsin D","volume":"34","author":"Evin","year":"1995","journal-title":"Biochemistry"},{"key":"10.3233\/JAD-151186_ref37","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/S1357-2725(99)00053-9","article-title":"In vitro processing of amyloid precursor protein by cathepsin D","volume":"31","author":"Sadik","year":"1999","journal-title":"Int J Biochem Cell Biol"},{"key":"10.3233\/JAD-151186_ref38","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/j.1471-4159.2009.06528.x","article-title":"BACE1 and BACE2 enzymatic activities in Alzheimer\u2019s disease","volume":"112","author":"Ahmed","year":"2010","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-151186_ref39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0006-8993(96)01330-3","article-title":"Cathepsin D displays in vitro beta-secretase-like specificity","volume":"750","author":"Chevallier","year":"1997","journal-title":"Brain Res"},{"key":"10.3233\/JAD-151186_ref40","first-page":"89","article-title":"Some properties of cathepsin E from bovine spleen","volume":"34","author":"Turk","year":"1968","journal-title":"Enzymologia"},{"key":"10.3233\/JAD-151186_ref41","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1126\/science.286.5440.735","article-title":"Beta-secretase cleavage of Alzheimer\u2019s amyloid precursor protein by the transmembrane aspartic protease BACE","volume":"286","author":"Vassar","year":"1999","journal-title":"Science"},{"key":"10.3233\/JAD-151186_ref42","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/cr.2010.3","article-title":"A GPCR\/secretase complex regulates beta- and gamma-secretase specificity for Abeta production and contributes to AD pathogenesis","volume":"20","author":"Teng","year":"2010","journal-title":"Cell Res"},{"key":"10.3233\/JAD-151186_ref43","doi-asserted-by":"crossref","first-page":"5425","DOI":"10.1523\/JNEUROSCI.23-13-05425.2003","article-title":"Proteolytic processing of the p75 neurotrophin receptor and two homologs generates C-terminal fragments with signaling capability","volume":"23","author":"Kanning","year":"2003","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-151186_ref44","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1242\/jcs.01263","article-title":"Release of a membrane-bound death domain by gamma-secretase processing of the p75NTR homolog NRADD","volume":"117","author":"Gowrishankar","year":"2004","journal-title":"J Cell Sci"},{"key":"10.3233\/JAD-151186_ref45","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s00018-008-7462-2","article-title":"Substrate specificity of gamma-secretase and other intramembrane proteases","volume":"65","author":"Beel","year":"2008","journal-title":"Cell Mol Life Sci"},{"key":"10.3233\/JAD-151186_ref46","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1086\/302553","article-title":"Early-onset autosomal dominant Alzheimer disease: Prevalence, genetic heterogeneity, and mutation spectrum","volume":"65","author":"Campion","year":"1999","journal-title":"Am J Hum Genet"},{"key":"10.3233\/JAD-151186_ref47","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1002\/humu.22117","article-title":"Locus-specific mutation databases for neurodegenerative brain diseases","volume":"33","author":"Cruts","year":"2012","journal-title":"Hum Mutat"},{"key":"10.3233\/JAD-151186_ref48","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/1531-8249(200101)49:1<125::AID-ANA21>3.0.CO;2-1","article-title":"Variable phenotype of Alzheimer\u2019s disease with spastic paraparesis","volume":"49","author":"Smith","year":"2001","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-151186_ref49","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1093\/hmg\/8.8.1529","article-title":"Aberrant splicing in the presenilin-1 intron 4 mutation causes presenile Alzheimer\u2019s disease by increased Abeta42 secretion","volume":"8","author":"De Jonghe","year":"1999","journal-title":"Hum Mol Genet"},{"key":"10.3233\/JAD-151186_ref50","doi-asserted-by":"crossref","first-page":"7615","DOI":"10.1074\/jbc.274.12.7615","article-title":"The biological and pathological function of the presenilin-1 Deltaexon 9 mutation is independent of its defect to undergo proteolytic processing","volume":"274","author":"Steiner","year":"1999","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref51","first-page":"S277","article-title":"Presenilin-1 mutation (L271V) results in altered exon 8 splicing and Alzheimer\u2019s disease with non-cored plaques and no neuritic dystrophy","volume":"23","author":"Kwok","year":"2002","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-151186_ref52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12017-009-8104-z","article-title":"An overview of APP processing enzymes and products","volume":"12","author":"Chow","year":"2010","journal-title":"Neuromolecular Med"},{"key":"10.3233\/JAD-151186_ref53","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1471-2091-3-25","article-title":"Pro-domain removal in ASP-2 and the cleavage of the amyloid precursor are influenced by pH","volume":"3","author":"Sidera","year":"2002","journal-title":"BMC Biochem"},{"key":"10.3233\/JAD-151186_ref54","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/embo-reports\/kve180","article-title":"Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch","volume":"2","author":"Sastre","year":"2001","journal-title":"EMBO Rep"},{"key":"10.3233\/JAD-151186_ref55","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1074\/jbc.M005968200","article-title":"A novel gamma -secretase assay based on detection of the putative C-terminal fragment-gamma of amyloid beta protein precursor","volume":"276","author":"Pinnix","year":"2001","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref56","doi-asserted-by":"crossref","first-page":"35235","DOI":"10.1074\/jbc.C100357200","article-title":"Distinct intramembrane cleavage of the beta-amyloid precursor protein family resembling gamma-secretase-like cleavage of Notch","volume":"276","author":"Gu","year":"2001","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref57","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1111\/j.1471-4159.2010.07044.x","article-title":"Phosphorylation of APP-CTF-AICD domains and interaction with adaptor proteins: Signal transduction and\/or transcriptional role\u2013relevance for Alzheimer pathology","volume":"115","author":"Schettini","year":"2010","journal-title":"J Neurochem"},{"issue":"Suppl 1","key":"10.3233\/JAD-151186_ref58","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1471-4159.2011.07475.x","article-title":"The physiology of the beta-amyloid precursor protein intracellular domain AICD","volume":"120","author":"Pardossi-Piquard","year":"2012","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-151186_ref59","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1152\/physrev.00023.2009","article-title":"Proteases and proteolysis in Alzheimer disease: A multifactorial view on the disease process","volume":"90","author":"De Strooper","year":"2010","journal-title":"Physiol Rev"},{"key":"10.3233\/JAD-151186_ref60","doi-asserted-by":"crossref","first-page":"14776","DOI":"10.1074\/jbc.M513453200","article-title":"Equimolar production of amyloid beta-protein and amyloid precursor protein intracellular domain from beta-carboxyl-terminal fragment by gamma-secretase","volume":"281","author":"Kakuda","year":"2006","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref61","doi-asserted-by":"crossref","first-page":"13042","DOI":"10.1523\/JNEUROSCI.2362-09.2009","article-title":"gamma-Secretase: Successive tripeptide and tetrapeptide release from the transmembrane domain of beta-carboxyl terminal fragment","volume":"29","author":"Takami","year":"2009","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-151186_ref62","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/sj.embor.7400896","article-title":"When loss is gain: Reducedresenilin proteolytic function leads to increased Abeta42\/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease","volume":"8","author":"Wolfe","year":"2007","journal-title":"EMBO Rep"},{"key":"10.3233\/JAD-151186_ref63","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1038\/emboj.2012.79","article-title":"The mechanism of gamma-Secretase dysfunction in familial Alzheimer disease","volume":"31","author":"Chavez-Gutierrez","year":"2012","journal-title":"EMBO J"},{"key":"10.3233\/JAD-151186_ref64","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0896-6273(94)90458-8","article-title":"Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: Evidence that an initially deposited species is A beta 42(43)","volume":"13","author":"Iwatsubo","year":"1994","journal-title":"Neuron"},{"key":"10.3233\/JAD-151186_ref65","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1756-6606-3-7","article-title":"Presenilins and the gamma-secretase: Still a complex problem","volume":"3","author":"Small","year":"2010","journal-title":"Mol Brain"},{"key":"10.3233\/JAD-151186_ref66","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1194\/jlr.M400333-JLR200","article-title":"Association of active gamma-secretase complex with lipid rafts","volume":"46","author":"Urano","year":"2005","journal-title":"J Lipid Res"},{"key":"10.3233\/JAD-151186_ref67","doi-asserted-by":"crossref","first-page":"44945","DOI":"10.1074\/jbc.M407986200","article-title":"Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes","volume":"279","author":"Vetrivel","year":"2004","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref68","doi-asserted-by":"crossref","first-page":"21326","DOI":"10.1074\/jbc.M112.356659","article-title":"Generation of Alzheimer disease-associated amyloid beta42\/43 peptide by gamma-secretase can be inhibited directly by modulation of membrane thickness","volume":"287","author":"Winkler","year":"2012","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref69","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1084\/jem.20150892","article-title":"Qualitative changes in human gamma-secretase underlie familial Alzheimer\u2019s disease","volume":"212","author":"Szaruga","year":"2015","journal-title":"J Exp Med"},{"key":"10.3233\/JAD-151186_ref70","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1126\/science.1197623","article-title":"Decreased clearance of CNS beta-amyloid in Alzheimer\u2019s disease","volume":"330","author":"Mawuenyega","year":"2010","journal-title":"Science"},{"key":"10.3233\/JAD-151186_ref71","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.neuron.2015.02.010","article-title":"Presenilin-1 knockin mice reveal loss-of-function mechanism for familial Alzheimer\u2019s disease","volume":"85","author":"Xia","year":"2015","journal-title":"Neuron"},{"key":"10.3233\/JAD-151186_ref72","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3233\/JAD-2011-101065","article-title":"The many substrates of presenilin\/gamma-secretase","volume":"25","author":"Haapasalo","year":"2011","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-151186_ref73","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1523\/JNEUROSCI.0350-08.2008","article-title":"Beta-amyloid(1-42) induces neuronal death through the p75 neurotrophin receptor","volume":"28","author":"Sotthibundhu","year":"2008","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-151186_ref74","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S0092-8674(02)00970-4","article-title":"Presenilin couples the paired phosphorylation of beta-catenin independent of axin: Imlications for beta-catenin activation in tumorigenesis","volume":"110","author":"Kang","year":"2002","journal-title":"Cell"},{"key":"10.3233\/JAD-151186_ref75","doi-asserted-by":"crossref","first-page":"11606","DOI":"10.1523\/JNEUROSCI.0954-13.2013","article-title":"Trans-dominant negative effects of pathogenic PSEN1 mutations on gamma-secretase activity and Abeta production","volume":"33","author":"Heilig","year":"2013","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-151186_ref76","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.placenta.2007.01.012","article-title":"Method to enhance transfection efficiency of cell lines and placental fibroblasts","volume":"28","author":"Zhang","year":"2007","journal-title":"Placenta"},{"key":"10.3233\/JAD-151186_ref77","doi-asserted-by":"crossref","first-page":"28415","DOI":"10.1074\/jbc.272.45.28415","article-title":"Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors","volume":"272","author":"Thinakaran","year":"1997","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref79","doi-asserted-by":"crossref","first-page":"7853","DOI":"10.1523\/JNEUROSCI.1443-10.2010","article-title":"Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of gamma-secretase-mediated intramembrane proteolysis","volume":"30","author":"Fukumori","year":"2010","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-151186_ref80","doi-asserted-by":"crossref","first-page":"5085","DOI":"10.1523\/JNEUROSCI.0317-12.2012","article-title":"Familial frontotemporal dementia-associated presenilin-1 c.548G>T mutation causes decreased mRNA expression and reduced presenilin function in knock-in mice","volume":"32","author":"Watanabe","year":"2012","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-151186_ref81","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ana.20083","article-title":"A novel presenilin 1 mutation associated with Pick\u2019s disease but not beta-amyloid plaques","volume":"55","author":"Dermaut","year":"2004","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-151186_ref82","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1016\/S0197-4580(04)80206-9","article-title":"A novel presenilin 1 mutation (Gly183Val) is associated with Pick\u2019s disease in the absence of beta-amyloid plaques","volume":"25","author":"Dermaut","year":"2004","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-151186_ref83","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.tig.2005.09.005","article-title":"Tau is central in the genetic Alzheimer-frontotemporal dementia spectrum","volume":"21","author":"Dermaut","year":"2005","journal-title":"Trends Genet"},{"key":"10.3233\/JAD-151186_ref84","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1097\/00001756-200205070-00036","article-title":"Alternative transcripts of presenilin-1 associated with frontotemporal dementia","volume":"13","author":"Evin","year":"2002","journal-title":"Neuroreport"},{"key":"10.3233\/JAD-151186_ref85","doi-asserted-by":"crossref","first-page":"9637","DOI":"10.1073\/pnas.95.16.9637","article-title":"Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau","volume":"95","author":"Takashima","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-151186_ref86","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0896-6273(04)00182-5","article-title":"Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration","volume":"42","author":"Saura","year":"2004","journal-title":"Neuron"},{"key":"10.3233\/JAD-151186_ref87","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1093\/hmg\/ddt448","article-title":"Differential, dominant activation and inhibition of Notch signalling and APP cleavage by truncations of PSEN1 in human disease","volume":"23","author":"Newman","year":"2014","journal-title":"Hum Mol Genet"},{"key":"10.3233\/JAD-151186_ref88","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/nature14892","article-title":"An atomic structure of human gamma-secretase","volume":"525","author":"Bai","year":"2015","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref89","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.1196284","article-title":"Gamma-secretase gene mutations in familial acne inversa","volume":"330","author":"Wang","year":"2010","journal-title":"Science"},{"key":"10.3233\/JAD-151186_ref90","doi-asserted-by":"crossref","first-page":"13075","DOI":"10.1073\/pnas.1735338100","article-title":"A presenilin dimer at the core of the gamma-secretase enzyme: Insights from parallel analysis of Notch 1 and APP proteolysis","volume":"100","author":"Schroeter","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-151186_ref91","doi-asserted-by":"crossref","first-page":"17042","DOI":"10.1038\/srep17042","article-title":"Physiologically generated presenilin 1 lacking exon 8 fails to rescue brain PS1-\/- phenotype and forms complexes with wildtype PS1 and nicastrin","volume":"5","author":"Brautigam","year":"2015","journal-title":"Sci Rep"},{"key":"10.3233\/JAD-151186_ref92","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.cell.2010.05.008","article-title":"Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations","volume":"141","author":"Lee","year":"2010","journal-title":"Cell"},{"key":"10.3233\/JAD-151186_ref93","doi-asserted-by":"crossref","first-page":"8633","DOI":"10.1523\/JNEUROSCI.0556-12.2012","article-title":"A role for presenilins in autophagy revisited: Normal acidification of lysosomes in cells lacking PSEN1 and PSEN2","volume":"32","author":"Zhang","year":"2012","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-151186_ref94","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1083\/jcb.201201076","article-title":"Lysosomal calcium homeostasis defects, not proton pump defects, cause endo-lysosomal dysfunction in PSEN-deficient cells","volume":"198","author":"Coen","year":"2012","journal-title":"J Cell Biol"},{"key":"10.3233\/JAD-151186_ref96","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1111\/ejn.12169","article-title":"Autophagy failure in Alzheimer\u2019s disease and the role of defective lysosomal acidification","volume":"37","author":"Wolfe","year":"2013","journal-title":"Eur J Neurosci"},{"key":"10.3233\/JAD-151186_ref97","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1093\/jnen\/63.8.821","article-title":"Presenilin mutations in familial Alzheimer disease and transgenic mouse models accelerate neuronal lysosomal pathology","volume":"63","author":"Cataldo","year":"2004","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.3233\/JAD-151186_ref98","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/jnen\/64.2.113","article-title":"Extensive involvement of autophagy in Alzheimer disease: An immuno-electron microscopy study","volume":"64","author":"Nixon","year":"2005","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.3233\/JAD-151186_ref99","doi-asserted-by":"crossref","first-page":"D82","DOI":"10.1093\/nar\/gku1163","article-title":"COXPRESdb in 2015: Coexpression database for animal species by DNA-microarray and RNAseq-based expression data with multiple quality assessment systems","volume":"43","author":"Okamura","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"10.3233\/JAD-151186_ref100","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/ng.440","article-title":"Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer\u2019s disease","volume":"41","author":"Harold","year":"2009","journal-title":"Nat Genet"},{"key":"10.3233\/JAD-151186_ref101","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1001\/jama.2010.574","article-title":"Genome-wide analysis of genetic loci associated with Alzheimer disease","volume":"303","author":"Seshadri","year":"2010","journal-title":"JAMA"},{"key":"10.3233\/JAD-151186_ref102","doi-asserted-by":"crossref","first-page":"e1004606","DOI":"10.1371\/journal.pgen.1004606","article-title":"Genome-wide association meta-analysis of neuropathologic features of Alzheimer\u2019s disease and related dementias","volume":"10","author":"Beecham","year":"2014","journal-title":"PLoS Genet"},{"key":"10.3233\/JAD-151186_ref103","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1001\/jamaneurol.2014.1491","article-title":"Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: A genome-wide association study","volume":"71","author":"Naj","year":"2014","journal-title":"JAMA Neurol"},{"key":"10.3233\/JAD-151186_ref104","doi-asserted-by":"crossref","first-page":"4998","DOI":"10.1038\/ncomms5998","article-title":"PICALM modulates autophagy activity and tau accumulation","volume":"5","author":"Moreau","year":"2014","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-151186_ref105","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1046\/j.1471-4159.1999.0722498.x","article-title":"A novel presenilin-2 splice variant in human Alzheimer\u2019s disease brain tissue","volume":"72","author":"Sato","year":"1999","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-151186_ref106","doi-asserted-by":"crossref","first-page":"e66235","DOI":"10.1371\/journal.pone.0066235","article-title":"The guinea pig as a model for sporadic Alzheimer\u2019s disease (AD): the impact of cholesterol intake on expression of AD-related genes","volume":"8","author":"Sharman","year":"2013","journal-title":"PLoS One"},{"key":"10.3233\/JAD-151186_ref107","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1074\/jbc.M006886200","article-title":"Increased production of beta-amyloid and vulnerability to endoplasmic reticulum stress by an aberrant spliced form of presenilin 2","volume":"276","author":"Sato","year":"2001","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref108","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1093\/hmg\/ddv110","article-title":"Alzheimer\u2019s disease-related peptide PS2V plays ancient, conserved roles in suppression of the unfolded protein response under hypoxia and stimulation of gamma-secretase activity","volume":"24","author":"Moussavi Nik","year":"2015","journal-title":"Hum Mol Genet"},{"key":"10.3233\/JAD-151186_ref109","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.cell.2006.06.059","article-title":"Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer\u2019s disease-linked mutations","volume":"126","author":"Tu","year":"2006","journal-title":"Cell"},{"key":"10.3233\/JAD-151186_ref110","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.2353\/ajpath.2009.090219","article-title":"Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria","volume":"175","author":"Area-Gomez","year":"2009","journal-title":"Am J Pathol"},{"key":"10.3233\/JAD-151186_ref111","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.bbamem.2010.04.009","article-title":"Oxidative protein folding in the endoplasmic reticulum: Tight links to the mitochondria-associated membrane (MAM)","volume":"1798","author":"Simmen","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"10.3233\/JAD-151186_ref112","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1038\/emboj.2012.202","article-title":"Upregulated function of mitochondria-associated ER membranes in Alzheimer disease","volume":"31","author":"Area-Gomez","year":"2012","journal-title":"EMBO J"},{"key":"10.3233\/JAD-151186_ref113","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.bbamcr.2012.04.013","article-title":"Where the endoplasmic reticulum and the mitochondrion tie the knot: The mitochondria-associated membrane (MAM)","volume":"1833","author":"Raturi","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"10.3233\/JAD-151186_ref114","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nature11910","article-title":"Autophagosomes form at ER-mitochondria contact sites","volume":"495","author":"Hamasaki","year":"2013","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref115","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/ni.2550","article-title":"Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome","volume":"14","author":"Misawa","year":"2013","journal-title":"Nat Immunol"},{"key":"10.3233\/JAD-151186_ref116","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.mcn.2012.07.011","article-title":"Mitochondria-associated ER membranes in Alzheimer disease","volume":"55","author":"Schon","year":"2013","journal-title":"Mol Cell Neurosci"},{"key":"10.3233\/JAD-151186_ref117","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jchemneu.2003.12.004","article-title":"Induction of neuronal death by ER stress in Alzheimer\u2019s disease","volume":"28","author":"Katayama","year":"2004","journal-title":"J Chem Neuroanat"},{"key":"10.3233\/JAD-151186_ref118","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.celrep.2013.08.042","article-title":"Abeta secretion and plaque formation depend on autophagy","volume":"5","author":"Nilsson","year":"2013","journal-title":"Cell Rep"},{"key":"10.3233\/JAD-151186_ref119","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/bies.201400002","article-title":"Dual roles for autophagy: Degradation and secretion of Alzheimer\u2019s disease Abeta peptide","volume":"36","author":"Nilsson","year":"2014","journal-title":"Bioessays"},{"key":"10.3233\/JAD-151186_ref120","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1089\/dna.2014.2757","article-title":"Alzheimer\u2019s disease-related misfolded proteins and dysfunctional organelles on autophagy menu","volume":"34","author":"Correia","year":"2015","journal-title":"DNA Cell Biol"},{"key":"10.3233\/JAD-151186_ref121","first-page":"189","article-title":"Novel mutations in the amyloid precursor protein gene within Moroccan patients with Alzheimer\u2019s disease","volume":"53","author":"El Kadmiri","year":"2014","journal-title":"J Mol Neurosci"},{"key":"10.3233\/JAD-151186_ref122","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.neuroscience.2014.03.052","article-title":"Novel presenilin mutations within Moroccan patients with Early-Onset Alzheimer\u2019s Disease","volume":"269","author":"El Kadmiri","year":"2014","journal-title":"Neuroscience"},{"key":"10.3233\/JAD-151186_ref123","first-page":"1163","article-title":"Mutations in presenilin 2 and its implications in Alzheimer\u2019s disease and other dementia-associated disorders","volume":"10","author":"Cai","year":"2015","journal-title":"Clin Interv Aging"},{"key":"10.3233\/JAD-151186_ref124","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1242\/jcs.019265","article-title":"Autophagy, amyloidogenesis and Alzheimer disease","volume":"120","author":"Nixon","year":"2007","journal-title":"J Cell Sci"},{"key":"10.3233\/JAD-151186_ref125","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.cell.2010.08.014","article-title":"Iron-export ferroxidase activity of beta-amyloid precursor protein is inhibited by zinc in Alzheimer\u2019s disease","volume":"142","author":"Duce","year":"2010","journal-title":"Cell"},{"key":"10.3233\/JAD-151186_ref126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2009.07.041","article-title":"Amyloid precursor protein is required for convergent-extension movements during Zebrafish development","volume":"335","author":"Joshi","year":"2009","journal-title":"Dev Biol"},{"key":"10.3233\/JAD-151186_ref127","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/dvdy.23725","article-title":"Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins","volume":"241","author":"Liao","year":"2012","journal-title":"Dev Dyn"},{"key":"10.3233\/JAD-151186_ref128","doi-asserted-by":"crossref","first-page":"e75052","DOI":"10.1371\/journal.pone.0075052","article-title":"Amyloid-beta and APP deficiencies cause severe cerebrovascular defects: Important work for an old villain","volume":"8","author":"Luna","year":"2013","journal-title":"PLoS One"},{"key":"10.3233\/JAD-151186_ref129","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/jcp.24835","article-title":"Amyloid precursor protein (APP) affects global protein synthesis in dividing human cells","volume":"230","author":"Sobol","year":"2015","journal-title":"J Cell Physiol"},{"key":"10.3233\/JAD-151186_ref130","doi-asserted-by":"crossref","first-page":"e34209","DOI":"10.1371\/journal.pone.0034209","article-title":"Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth","volume":"7","author":"Song","year":"2012","journal-title":"PLoS One"},{"key":"10.3233\/JAD-151186_ref131","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/nature07767","article-title":"APP binds DR6 to trigger axon pruning and neuron death via distinct caspases","volume":"457","author":"Nikolaev","year":"2009","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref132","doi-asserted-by":"crossref","first-page":"e0140210","DOI":"10.1371\/journal.pone.0140210","article-title":"Altered innate immune and glial cell responses to inflammatory stimuli in amyloid precursor protein knockout mice","volume":"10","author":"Carrano","year":"2015","journal-title":"PLoS One"},{"key":"10.3233\/JAD-151186_ref133","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fnagi.2015.00077","article-title":"APP intracellular domain derived from amyloidogenic beta- and gamma-secretase cleavage regulates neprilysin expression","volume":"7","author":"Grimm","year":"2015","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-151186_ref134","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/jnc.12680","article-title":"The Abeta-clearance protein transthyretin, like neprilysin, is epigenetically regulated by the amyloid precursor protein intracellular domain","volume":"130","author":"Kerridge","year":"2014","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-151186_ref135","doi-asserted-by":"crossref","first-page":"9776","DOI":"10.1074\/jbc.M110.163964","article-title":"Presenilins promote the cellular uptake of copper and zinc and maintain copper chaperone of SOD1-dependent copper\/zinc superoxide dismutase activity","volume":"286","author":"Greenough","year":"2011","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref136","doi-asserted-by":"crossref","unstructured":"Agrawal V , Sawhney N , Hickey E , McCarthy JV (2015) Loss of presenilin 2 function is associated with defective LPS-mediated innate immune responsiveness. Mol Neurobiol, doi: 10.1007\/s12035-015-9285-0","DOI":"10.1007\/s12035-015-9285-0"},{"key":"10.3233\/JAD-151186_ref137","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/alzrt258","article-title":"Truncated and modified amyloid-beta species","volume":"6","author":"Kummer","year":"2014","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-151186_ref138","first-page":"1121","article-title":"The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease","volume":"115","author":"Gandy","year":"2005","journal-title":"J Clin Invest"},{"key":"10.3233\/JAD-151186_ref139","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00221-011-2932-4","article-title":"Roles of amyloid precursor protein family members in neuroprotection, stress signaling and aging","volume":"217","author":"Kogel","year":"2012","journal-title":"Exp Brain Res"},{"key":"10.3233\/JAD-151186_ref140","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/S0891-5849(01)00688-8","article-title":"Amyloid-beta: An antioxidant that becomes a pro-oxidant and critically contributes to Alzheimer\u2019s disease","volume":"31","author":"Kontush","year":"2001","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-151186_ref141","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1080\/10715760100301521","article-title":"Resistance of human cerebrospinal fluid to in vitro oxidation is directly related to its amyloid-beta content","volume":"35","author":"Kontush","year":"2001","journal-title":"Free Radic Res"},{"key":"10.3233\/JAD-151186_ref142","doi-asserted-by":"crossref","first-page":"11653","DOI":"10.1021\/bi8011093","article-title":"Amyloid beta-Cu2+ complexes in both monomeric and fibrillar forms do not generate H2O2 catalytically but quench hydroxyl radicals","volume":"47","author":"Nadal","year":"2008","journal-title":"Biochemistry"},{"key":"10.3233\/JAD-151186_ref143","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/S0891-5849(02)01021-3","article-title":"Amyloid-beta and tau serve antioxidant functions in the aging and Alzheimer brain","volume":"33","author":"Smith","year":"2002","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-151186_ref144","doi-asserted-by":"crossref","first-page":"4354","DOI":"10.1021\/bi802361k","article-title":"Abeta40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems","volume":"48","author":"Baruch-Suchodolsky","year":"2009","journal-title":"Biochemistry"},{"key":"10.3233\/JAD-151186_ref145","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-0173(03)00174-7","article-title":"Amyloid-beta: A chameleon walking in two worlds: A review of the trophic and toxic properties of amyloid-beta","volume":"43","author":"Atwood","year":"2003","journal-title":"Brain Res Brain Res Rev"},{"key":"10.3233\/JAD-151186_ref146","doi-asserted-by":"crossref","first-page":"e39598","DOI":"10.1371\/journal.pone.0039598","article-title":"Alzheimer\u2019s-related peptide amyloid-beta plays a conserved role in angiogenesis","volume":"7","author":"Cameron","year":"2012","journal-title":"PLoS One"},{"key":"10.3233\/JAD-151186_ref147","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1750-1326-5-15","article-title":"Soluble amyloid-beta, effect on cerebral arteriolar regulation and vascular cells","volume":"5","author":"Dietrich","year":"2010","journal-title":"Mol Neurodegener"},{"key":"10.3233\/JAD-151186_ref148","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/416535a","article-title":"Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo","volume":"416","author":"Walsh","year":"2002","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref149","doi-asserted-by":"crossref","first-page":"e9505","DOI":"10.1371\/journal.pone.0009505","article-title":"The Alzheimer\u2019s disease-associated amyloid beta-protein is an antimicrobial peptide","volume":"5","author":"Soscia","year":"2010","journal-title":"PLoS One"},{"key":"10.3233\/JAD-151186_ref150","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.gene.2011.06.017","article-title":"Functional activity of the novel Alzheimer\u2019s amyloid beta-peptide interacting domain (AbetaID) in the APP and BACE1 promoter sequences and implications in activating apoptotic genes and in amyloidogenesis","volume":"488","author":"Bailey","year":"2011","journal-title":"Gene"},{"key":"10.3233\/JAD-151186_ref151","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2011.06.004","article-title":"The Alzheimer\u2019s amyloid beta-peptide (Abeta) binds a specific DNA Abeta-interacting domain (AbetaID) in the APP, BACE1, and APOE promoters in a sequence-specific manner: Characterizing a new regulatory motif","volume":"488","author":"Maloney","year":"2011","journal-title":"Gene"},{"key":"10.3233\/JAD-151186_ref152","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1111\/j.1471-4159.2012.07834.x","article-title":"beta-amyloid 1-42 induces physiological transcriptional regulation of BACE1","volume":"122","author":"Piccini","year":"2012","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-151186_ref153","doi-asserted-by":"crossref","first-page":"20182","DOI":"10.1074\/jbc.M114.564690","article-title":"Nuclear translocation uncovers the amyloid Peptide abeta42 as a regulator of gene transcription","volume":"289","author":"Barucker","year":"2014","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref154","doi-asserted-by":"crossref","first-page":"18727","DOI":"10.1073\/pnas.0606298103","article-title":"Hypoxia facilitates Alzheimer\u2019s disease pathogenesis by up-regulating BACE1 gene expression","volume":"103","author":"Sun","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-151186_ref155","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/j.1471-4159.2008.05858.x","article-title":"The up-regulation of BACE1 mediated by hypoxia and ischemic injury: Role of oxidative stress and HIF1alpha","volume":"108","author":"Guglielmotto","year":"2009","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-151186_ref156","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/j.1471-4159.2007.05072.x","article-title":"Oxidative stress activates a positive feedback between the gamma- and beta-secretase cleavages of the beta-amyloid precursor protein","volume":"104","author":"Tamagno","year":"2008","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-151186_ref157","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3233\/JAD-2011-110533","article-title":"The BACE1-PSEN-AbetaPP regulatory axis has an ancient role in response to low oxygen\/oxidative stress","volume":"28","author":"Moussavi Nik","year":"2012","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-151186_ref158","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1096\/fj.05-4986com","article-title":"Control of APP processing and Abeta generation level by BACE1 enzymatic activity and transcription","volume":"20","author":"Li","year":"2006","journal-title":"FASEB J"},{"key":"10.3233\/JAD-151186_ref159","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nature11283","article-title":"A mutation in APP protects against Alzheimer\u2019s disease and age-related cognitive decline","volume":"488","author":"Jonsson","year":"2012","journal-title":"Nature"},{"key":"10.3233\/JAD-151186_ref160","doi-asserted-by":"crossref","first-page":"e114633","DOI":"10.1371\/journal.pone.0114633","article-title":"Non-steroidal anti-inflammatory drugs use is associated with reduced risk of inflammation-associated cancers: NIH-AARP study","volume":"9","author":"Shebl","year":"2014","journal-title":"PLoS One"},{"key":"10.3233\/JAD-151186_ref161","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/jid.2014.312","article-title":"beta2-adrenoceptor activation modulates skin wound healing processes to reduce scarring","volume":"135","author":"Le Provost","year":"2015","journal-title":"J Invest Dermatol"},{"key":"10.3233\/JAD-151186_ref162","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1111\/ejn.12235","article-title":"Amyloid-beta protein (Abeta) Glu11 is the major beta-secretase site of beta-site amyloid-beta precursor protein-cleaving enzyme 1(BACE1), and shifting the cleavage site to Abeta Asp1 contributes to Alzheimer pathogenesis","volume":"37","author":"Deng","year":"2013","journal-title":"Eur J Neurosci"},{"key":"10.3233\/JAD-151186_ref163","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.celrep.2014.07.028","article-title":"Nontranscriptional role of Hif-1alpha in activation of gamma-secretase and notch signaling in breast cancer","volume":"8","author":"Villa","year":"2014","journal-title":"Cell Rep"},{"key":"10.3233\/JAD-151186_ref164","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1002\/jnr.23634","article-title":"Evidence of neurodegeneration in obstructive sleep apnea: Relationship between obstructive sleep apnea and cognitive dysfunction in the elderly","volume":"93","author":"Daulatzai","year":"2015","journal-title":"J Neurosci Res"},{"key":"10.3233\/JAD-151186_ref165","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1038\/tp.2011.55","article-title":"Metabolome in progression to Alzheimer\u2019s disease","volume":"1","author":"Oresic","year":"2011","journal-title":"Transl Psychiatry"},{"key":"10.3233\/JAD-151186_ref166","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/cbin.10463","article-title":"Signaling pathways and mechanisms of hypoxia-induced autophagy in the animal cells","volume":"39","author":"Fang","year":"2015","journal-title":"Cell Biol Int"},{"key":"10.3233\/JAD-151186_ref167","doi-asserted-by":"crossref","first-page":"353","DOI":"10.2353\/ajpath.2010.090482","article-title":"Age-related vascular pathology in transgenic mice expressing presenilin 1-associated familial Alzheimer\u2019s disease mutations","volume":"176","author":"Gama Sosa","year":"2010","journal-title":"Am J Pathol"},{"key":"10.3233\/JAD-151186_ref168","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0304-3940(99)00239-6","article-title":"Intravascular beta-amyloid infusion increases blood pressure: Implications for a vasoactive role of beta-amyloid in the pathogenesis of Alzheimer\u2019s disease","volume":"268","author":"Arendash","year":"1999","journal-title":"Neurosci Lett"},{"key":"10.3233\/JAD-151186_ref169","doi-asserted-by":"crossref","first-page":"10873","DOI":"10.1074\/jbc.M608856200","article-title":"Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation","volume":"282","author":"Zhang","year":"2007","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-151186_ref170","doi-asserted-by":"crossref","first-page":"e28263","DOI":"10.1371\/journal.pone.0028263","article-title":"Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid beta levels in humans","volume":"6","author":"Zetterberg","year":"2011","journal-title":"PLoS One"},{"key":"10.3233\/JAD-151186_ref171","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1474-4422(13)70044-9","article-title":"Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer\u2019s disease: A prospective cohort study","volume":"12","author":"Villemagne","year":"2013","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-151186_ref172","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.nbd.2015.08.014","article-title":"Vascular dysfunction in the pathogenesis of Alzheimer\u2019s disease - A review of endothelium-mediated mechanisms and ensuing vicious circles","volume":"82","author":"Di Marco","year":"2015","journal-title":"Neurobiol Dis"},{"key":"10.3233\/JAD-151186_ref173","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.neurobiolaging.2004.08.002","article-title":"Mean age of onset in familial Alzheimer\u2019s disease is determined by amyloid beta 42","volume":"26","author":"Duering","year":"2005","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-151186_ref174","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/humu.20336","article-title":"Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40","volume":"27","author":"Kumar-Singh","year":"2006","journal-title":"Hum Mutat"},{"key":"10.3233\/JAD-151186_ref175","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/nm0997-1021","article-title":"Alzheimer\u2019s A beta(1-42) is generated in the endoplasmic reticulum\/intermediate compartment of NT2N cells","volume":"3","author":"Cook","year":"1997","journal-title":"Nat Med"},{"key":"10.3233\/JAD-151186_ref176","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/nm0997-1016","article-title":"Distinct sites of intracellular production for Alzheimer\u2019s disease A beta40\/42 amyloid peptides","volume":"3","author":"Hartmann","year":"1997","journal-title":"Nat Med"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-151186","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:02:46Z","timestamp":1777370566000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-151186"}},"subtitle":[],"editor":[{"given":"M. Paul","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,5,23]]},"references-count":174,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.3233\/jad-151186","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,23]]}}}