{"id":"https://openalex.org/W2152868080","doi":"https://doi.org/10.1177/1073858410366162","title":"An Amyloid-Notch Hypothesis for Alzheimer\u2019s Disease","display_name":"An Amyloid-Notch Hypothesis for Alzheimer\u2019s Disease","publication_year":2010,"publication_date":"2010-06-30","ids":{"openalex":"https://openalex.org/W2152868080","doi":"https://doi.org/10.1177/1073858410366162","mag":"2152868080","pmid":"https://pubmed.ncbi.nlm.nih.gov/20592273"},"language":"en","primary_location":{"id":"doi:10.1177/1073858410366162","doi":"https://doi.org/10.1177/1073858410366162","is_oa":false,"landing_page_url":"https://doi.org/10.1177/1073858410366162","pdf_url":null,"source":{"id":"https://openalex.org/S103928886","display_name":"The Neuroscientist","issn_l":"1073-8584","issn":["1073-8584","1089-4098"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320017","host_organization_name":"SAGE Publishing","host_organization_lineage":["https://openalex.org/P4310320017"],"host_organization_lineage_names":["SAGE Publishing"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Neuroscientist","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5079722104","display_name":"Douglas W. Ethell","orcid":"https://orcid.org/0000-0002-9237-0265","observed_orcids":["https://orcid.org/0000-0002-9237-0265"]},"institutions":[{"id":"https://openalex.org/I103635307","display_name":"University of California, Riverside","ror":"https://ror.org/03nawhv43","country_code":"US","type":"education","lineage":["https://openalex.org/I103635307"]},{"id":"https://openalex.org/I93393672","display_name":"Western University of Health Sciences","ror":"https://ror.org/05167c961","country_code":"US","type":"education","lineage":["https://openalex.org/I93393672"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Douglas W. Ethell","raw_affiliation_strings":["Division of Biomedical Sciences/Neuroscience, University of California Riverside, Riverside, and College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Biomedical Sciences/Neuroscience, University of California Riverside, Riverside, and College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA,","institution_ids":["https://openalex.org/I103635307","https://openalex.org/I93393672"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5079722104"],"corresponding_institution_ids":["https://openalex.org/I103635307","https://openalex.org/I93393672"],"apc_list":{"value":4400,"currency":"USD","value_usd":4400},"apc_paid":null,"fwci":1.4697,"has_fulltext":false,"cited_by_count":39,"citation_normalized_percentile":{"value":0.79400375,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":98},"biblio":{"volume":"16","issue":"6","first_page":"614","last_page":"617"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11266","display_name":"Neuroinflammation and Neurodegeneration Mechanisms","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2808","display_name":"Neurology"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10009","display_name":"Dementia and Cognitive Impairment Research","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2738","display_name":"Psychiatry and Mental health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/alzheimer-s-disease","display_name":"Alzheimer's disease","score":0.9829999804496765},{"id":"https://openalex.org/keywords/amyloid-hypothesis","display_name":"amyloid hypothesis","score":0.9169999957084656},{"id":"https://openalex.org/keywords/amyloid-beta","display_name":"amyloid-beta","score":0.9800000190734863},{"id":"https://openalex.org/keywords/notch-signaling","display_name":"Notch signaling","score":0.8259999752044678},{"id":"https://openalex.org/keywords/amyloid-precursor-protein","display_name":"amyloid precursor protein","score":0.8740000128746033},{"id":"https://openalex.org/keywords/gamma-secretase","display_name":"gamma-secretase","score":0.8690000176429749},{"id":"https://openalex.org/keywords/endothelial-tip-cells","display_name":"endothelial tip cells","score":0.7590000033378601},{"id":"https://openalex.org/keywords/blood-vessel-density","display_name":"blood vessel density","score":0.7089999914169312},{"id":"https://openalex.org/keywords/capillary-bed","display_name":"capillary network","score":0.6959999799728394},{"id":"https://openalex.org/keywords/ephb2","display_name":"EphB2","score":0.9129999876022339},{"id":"https://openalex.org/keywords/dendritic-spines","display_name":"dendritic spines","score":0.8679999709129333},{"id":"https://openalex.org/keywords/synapse-loss","display_name":"synaptic loss","score":0.9599999785423279},{"id":"https://openalex.org/keywords/gamma-secretase-inhibitors","display_name":"gamma-secretase inhibitors","score":0.8100000023841858},{"id":"https://openalex.org/keywords/clinical-trial-failure","display_name":"clinical trial failure","score":0.47699999809265137}],"concepts":[{"id":"https://openalex.org/C161879069","wikidata":"https://www.wikidata.org/wiki/Q904082","display_name":"Notch signaling pathway","level":3,"score":0.7916804552078247},{"id":"https://openalex.org/C36103677","wikidata":"https://www.wikidata.org/wiki/Q4749551","display_name":"Amyloid precursor protein secretase","level":5,"score":0.7128254175186157},{"id":"https://openalex.org/C31705614","wikidata":"https://www.wikidata.org/wiki/Q423510","display_name":"Amyloid precursor protein","level":4,"score":0.6235795021057129},{"id":"https://openalex.org/C2776878037","wikidata":"https://www.wikidata.org/wiki/Q169444","display_name":"Zebrafish","level":3,"score":0.5805433988571167},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5503765344619751},{"id":"https://openalex.org/C2777633098","wikidata":"https://www.wikidata.org/wiki/Q2736051","display_name":"Amyloid (mycology)","level":2,"score":0.5488527417182922},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.534175455570221},{"id":"https://openalex.org/C127445978","wikidata":"https://www.wikidata.org/wiki/Q187181","display_name":"Synapse","level":2,"score":0.48273250460624695},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4561629891395569},{"id":"https://openalex.org/C2778961482","wikidata":"https://www.wikidata.org/wiki/Q25241","display_name":"Vertebrate","level":3,"score":0.4482623338699341},{"id":"https://openalex.org/C180081513","wikidata":"https://www.wikidata.org/wiki/Q4914721","display_name":"Biochemistry of Alzheimer's disease","level":5,"score":0.4451243579387665},{"id":"https://openalex.org/C2778171954","wikidata":"https://www.wikidata.org/wiki/Q15328541","display_name":"Gamma secretase","level":2,"score":0.4395098388195038},{"id":"https://openalex.org/C2776156579","wikidata":"https://www.wikidata.org/wiki/Q417667","display_name":"Amyloid beta","level":3,"score":0.41878026723861694},{"id":"https://openalex.org/C2779822359","wikidata":"https://www.wikidata.org/wiki/Q2914458","display_name":"Interstitial fluid","level":2,"score":0.4127911329269409},{"id":"https://openalex.org/C502032728","wikidata":"https://www.wikidata.org/wiki/Q11081","display_name":"Alzheimer's disease","level":3,"score":0.36349397897720337},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.2982953190803528},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.24884939193725586},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.24276933073997498},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.2271789014339447},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.19962918758392334},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.14119145274162292},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.1073775589466095},{"id":"https://openalex.org/C59822182","wikidata":"https://www.wikidata.org/wiki/Q441","display_name":"Botany","level":1,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000544","descriptor_name":"Alzheimer Disease","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D000686","descriptor_name":"Amyloidosis","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000686","descriptor_name":"Amyloidosis","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D016229","descriptor_name":"Amyloid beta-Peptides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D051880","descriptor_name":"Receptors, Notch","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D053829","descriptor_name":"Amyloid Precursor Protein Secretases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1177/1073858410366162","doi":"https://doi.org/10.1177/1073858410366162","is_oa":false,"landing_page_url":"https://doi.org/10.1177/1073858410366162","pdf_url":null,"source":{"id":"https://openalex.org/S103928886","display_name":"The Neuroscientist","issn_l":"1073-8584","issn":["1073-8584","1089-4098"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320017","host_organization_name":"SAGE Publishing","host_organization_lineage":["https://openalex.org/P4310320017"],"host_organization_lineage_names":["SAGE Publishing"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Neuroscientist","raw_type":"journal-article"},{"id":"pmid:20592273","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/20592273","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":22,"referenced_works":["https://openalex.org/W1596429639","https://openalex.org/W1675018259","https://openalex.org/W1971162717","https://openalex.org/W1977570151","https://openalex.org/W1995946234","https://openalex.org/W2030020787","https://openalex.org/W2033302196","https://openalex.org/W2040490831","https://openalex.org/W2041622179","https://openalex.org/W2046402345","https://openalex.org/W2073551059","https://openalex.org/W2096410114","https://openalex.org/W2100618073","https://openalex.org/W2120860069","https://openalex.org/W2139595777","https://openalex.org/W2140912789","https://openalex.org/W2143338978","https://openalex.org/W2143485434","https://openalex.org/W2146417688","https://openalex.org/W2170159961","https://openalex.org/W2171883423","https://openalex.org/W4243693606"],"related_works":["https://openalex.org/W2018348569","https://openalex.org/W2056106881","https://openalex.org/W2093993008","https://openalex.org/W2989957010","https://openalex.org/W2279623439","https://openalex.org/W2030657258","https://openalex.org/W2061142513","https://openalex.org/W188237391","https://openalex.org/W2082694975","https://openalex.org/W7096701852"],"abstract_inverted_index":{"For":[0],"more":[1,118],"than":[2],"20":[3],"years,":[4],"the":[5,22,59,81,95,141,166,189],"amyloid":[6,41],"hypothesis":[7,185],"has":[8,51],"provided":[9],"an":[10,35],"important":[11],"framework":[12],"for":[13,165],"Alzheimer's":[14],"disease":[15],"(AD)":[16],"research,":[17],"yet":[18],"after":[19],"50,000":[20],"papers,":[21],"nonpathological":[23],"function":[24],"of":[25,37,72,85,91,143,168,192],"beta-amyloid":[26],"(A\u03b2)":[27],"remains":[28],"enigmatic.":[29],"This":[30,182],"mystery":[31],"is":[32],"compounded":[33],"by":[34,156],"absence":[36],"gross":[38],"abnormalities":[39],"in":[40,140,175],"precursor":[42],"protein":[43],"(APP)-deficient":[44],"mice":[45],"and":[46,67,102,130,146,172],"zebrafish":[47],"even":[48],"though":[49],"APP":[50,66],"been":[52],"highly":[53,119],"conserved":[54],"throughout":[55],"vertebrate":[56,63],"evolution.":[57],"Here,":[58],"author":[60],"hypothesizes":[61],"that":[62,116,135,178],"cells":[64,109],"express":[65],"release":[68],"A\u03b2":[69,92,100],"as":[70],"part":[71],"a":[73,112],"mechanism":[74],"to":[75,110,138,153],"optimize":[76],"blood":[77,121],"vessel":[78],"density":[79],"with":[80,196],"metabolite":[82],"removal":[83],"needs":[84],"local":[86],"tissue":[87],"neighborhoods.":[88],"High-gain":[89],"feedback":[90],"production":[93,101],"at":[94],"rate-limiting":[96],"\u03b3-secretase":[97,125,197],"step":[98],"reduces":[99],"Notch":[103,105,128,148],"activation.":[104],"inhibition":[106,149],"causes":[107],"endothelial":[108],"adopt":[111],"tip":[113],"cell":[114],"morphology":[115],"induces":[117],"branched":[120],"vessels.":[122],"In":[123],"vivo,":[124],"inhibitors":[126],"block":[127],"signaling":[129],"induce":[131],"dense":[132],"capillary":[133],"networks":[134],"are":[136,163],"similar":[137],"those":[139],"brains":[142],"AD":[144],"patients":[145],"mice.":[147],"could":[150],"also":[151,187],"contribute":[152],"synapse":[154],"loss":[155],"reducing":[157],"EphB2":[158],"receptor":[159],"expression.":[160],"EphB":[161],"receptors":[162],"critical":[164],"maintenance":[167],"dendritic":[169],"spine":[170],"morphology,":[171],"deficiencies":[173],"result":[174],"immature":[176],"spines":[177],"lack":[179],"synaptic":[180],"activity.":[181],"revised":[183],"amyloid-Notch":[184],"may":[186],"explain":[188],"disappointing":[190],"results":[191],"recent":[193],"clinical":[194],"trials":[195],"inhibitors.":[198]},"counts_by_year":[{"year":2025,"cited_by_count":2},{"year":2024,"cited_by_count":4},{"year":2021,"cited_by_count":6},{"year":2020,"cited_by_count":2},{"year":2019,"cited_by_count":1},{"year":2018,"cited_by_count":2},{"year":2017,"cited_by_count":2},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":2},{"year":2014,"cited_by_count":6},{"year":2013,"cited_by_count":6},{"year":2012,"cited_by_count":3}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}