{"id":"https://openalex.org/W4407369314","doi":"https://doi.org/10.7554/elife.102274","title":"Alzheimer-mutant \u03b3-secretase complexes stall amyloid \u03b2-peptide production","display_name":"Alzheimer-mutant \u03b3-secretase complexes stall amyloid \u03b2-peptide production","publication_year":2024,"publication_date":"2024-11-26","ids":{"openalex":"https://openalex.org/W4407369314","doi":"https://doi.org/10.7554/elife.102274","pmid":"https://pubmed.ncbi.nlm.nih.gov/39257787","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/11383658"},"language":"en","primary_location":{"id":"doi:10.7554/elife.102274","doi":"https://doi.org/10.7554/elife.102274","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.102274","pdf_url":"https://elifesciences.org/reviewed-preprints/102274.pdf","source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},"volume":null,"type":"preprint","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://elifesciences.org/reviewed-preprints/102274.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5106912507","display_name":"Parnian Arafi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I146416000","display_name":"University of Kansas","ror":"https://ror.org/001tmjg57","country_code":"US","type":"education","lineage":["https://openalex.org/I146416000"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Parnian Arafi","raw_affiliation_strings":["Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, USA","Department of Medicinal Chemistry, University of Kansas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, USA","institution_ids":["https://openalex.org/I146416000"]},{"raw_affiliation_string":"Department of Medicinal Chemistry, University of Kansas","institution_ids":["https://openalex.org/I146416000"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040533988","display_name":"Sujan Devkota","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I146416000","display_name":"University of Kansas","ror":"https://ror.org/001tmjg57","country_code":"US","type":"education","lineage":["https://openalex.org/I146416000"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sujan Devkota","raw_affiliation_strings":["Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, USA","Department of Medicinal Chemistry, University of Kansas"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, USA","institution_ids":["https://openalex.org/I146416000"]},{"raw_affiliation_string":"Department of Medicinal Chemistry, University of Kansas","institution_ids":["https://openalex.org/I146416000"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5104013281","display_name":"Emily M. Williams","orcid":"https://orcid.org/0000-0002-8262-9181","observed_orcids":["https://orcid.org/0000-0002-8262-9181"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Emily Williams","raw_affiliation_strings":["Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA","Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915"]},{"raw_affiliation_string":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5072516493","display_name":"Masato Maesako","orcid":"https://orcid.org/0000-0002-1970-2462","observed_orcids":["https://orcid.org/0000-0002-1970-2462"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Masato Maesako","raw_affiliation_strings":["Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA","Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School"],"raw_orcid":"https://orcid.org/0000-0002-1970-2462","affiliations":[{"raw_affiliation_string":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915"]},{"raw_affiliation_string":"Alzheimer Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5070207434","display_name":"Michael S. Wolfe","orcid":"https://orcid.org/0000-0002-5721-9092","observed_orcids":["https://orcid.org/0000-0002-5721-9092"]},"institutions":[{"id":"https://openalex.org/I146416000","display_name":"University of Kansas","ror":"https://ror.org/001tmjg57","country_code":"US","type":"education","lineage":["https://openalex.org/I146416000"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Michael S. Wolfe","raw_affiliation_strings":["Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, USA","Department of Medicinal Chemistry, University of Kansas"],"raw_orcid":"https://orcid.org/0000-0002-5721-9092","affiliations":[{"raw_affiliation_string":"Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, USA","institution_ids":["https://openalex.org/I146416000"]},{"raw_affiliation_string":"Department of Medicinal Chemistry, University of Kansas","institution_ids":["https://openalex.org/I146416000"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5070207434"],"corresponding_institution_ids":["https://openalex.org/I146416000"],"apc_list":{"value":3000,"currency":"USD","value_usd":2500},"apc_paid":{"value":3000,"currency":"USD","value_usd":2500},"fwci":null,"has_fulltext":true,"cited_by_count":8,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"13","issue":null,"first_page":null,"last_page":null},"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/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health 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"}},{"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"}}],"keywords":[{"id":"https://openalex.org/keywords/alzheimer-s-disease","display_name":"Alzheimer's disease","score":0.8009999990463257},{"id":"https://openalex.org/keywords/gamma-secretase","display_name":"gamma-secretase","score":0.75},{"id":"https://openalex.org/keywords/presenilin-1","display_name":"presenilin 1","score":0.9129999876022339},{"id":"https://openalex.org/keywords/amyloid-precursor-protein","display_name":"amyloid precursor protein","score":0.8489999771118164},{"id":"https://openalex.org/keywords/presenilin-1-mutations","display_name":"presenilin 1 mutations","score":0.6990000009536743},{"id":"https://openalex.org/keywords/amyloid-beta","display_name":"amyloid-beta","score":0.8429999947547913},{"id":"https://openalex.org/keywords/c99","display_name":"C99","score":0.675000011920929},{"id":"https://openalex.org/keywords/synaptic-degeneration","display_name":"synaptic degeneration","score":0.7429999709129333},{"id":"https://openalex.org/keywords/caenorhabditis-elegans-model","display_name":"Caenorhabditis elegans model","score":0.8220000267028809},{"id":"https://openalex.org/keywords/amyloid-hypothesis","display_name":"amyloid hypothesis","score":0.6830000281333923}],"concepts":[{"id":"https://openalex.org/C31705614","wikidata":"https://www.wikidata.org/wiki/Q423510","display_name":"Amyloid precursor protein","level":4,"score":0.6337981224060059},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.6265029311180115},{"id":"https://openalex.org/C36103677","wikidata":"https://www.wikidata.org/wiki/Q4749551","display_name":"Amyloid precursor protein secretase","level":5,"score":0.5684502124786377},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.5397130250930786},{"id":"https://openalex.org/C177907266","wikidata":"https://www.wikidata.org/wiki/Q17155455","display_name":"P3 peptide","level":5,"score":0.5187987685203552},{"id":"https://openalex.org/C41007966","wikidata":"https://www.wikidata.org/wiki/Q908080","display_name":"Alpha secretase","level":5,"score":0.48790428042411804},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.48000258207321167},{"id":"https://openalex.org/C2777633098","wikidata":"https://www.wikidata.org/wiki/Q2736051","display_name":"Amyloid (mycology)","level":2,"score":0.4683346748352051},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.45963436365127563},{"id":"https://openalex.org/C502032728","wikidata":"https://www.wikidata.org/wiki/Q11081","display_name":"Alzheimer's disease","level":3,"score":0.40002426505088806},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3359609842300415},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2917957305908203},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.11319279670715332},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.11017197370529175},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.09706535935401917},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.0},{"id":"https://openalex.org/C179104552","wikidata":"https://www.wikidata.org/wiki/Q11165","display_name":"Inorganic chemistry","level":1,"score":0.0}],"mesh":[],"locations_count":9,"locations":[{"id":"doi:10.7554/elife.102274","doi":"https://doi.org/10.7554/elife.102274","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.102274","pdf_url":"https://elifesciences.org/reviewed-preprints/102274.pdf","source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},{"id":"doi:10.7554/elife.102274.3","doi":"https://doi.org/10.7554/elife.102274.3","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.102274.3","pdf_url":null,"source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},{"id":"doi:10.1101/2024.08.30.610520","doi":"https://doi.org/10.1101/2024.08.30.610520","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2024.08.30.610520","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},{"id":"pmh:oai:pubmedcentral.nih.gov:11813224","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11813224","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11813224/pdf/elife-102274.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"Text"},{"id":"pmid:39257787","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/39257787","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":"bioRxiv : the preprint server for biology","raw_type":"Journal Article"},{"id":"pmid:39932776","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/39932776","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":"eLife","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:11383658","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11383658","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11383658/pdf/nihpp-2024.08.30.610520v2.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:916cc4b7e11343349f73ad61d31957a9","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/916cc4b7e11343349f73ad61d31957a9","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"eLife, Vol 13 (2025)","raw_type":"article"},{"id":"pmh:oai:kuscholarworks.ku.edu:1808/36250","doi":null,"is_oa":true,"landing_page_url":"https://hdl.handle.net/1808/36250","pdf_url":null,"source":{"id":"https://openalex.org/S4306400421","display_name":"KU ScholarWorks (The University of Kansas)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I146416000","host_organization_name":"University of Kansas","host_organization_lineage":["https://openalex.org/I146416000"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"13","raw_type":"Article"}],"best_oa_location":{"id":"doi:10.7554/elife.102274","doi":"https://doi.org/10.7554/elife.102274","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.102274","pdf_url":"https://elifesciences.org/reviewed-preprints/102274.pdf","source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.6240000128746033}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2172779308","display_name":"Leveraging Heterogeneity in Autosomal Dominant AD to Elucidate Pathophysiology and Improve AD Biomarkers","funder_award_id":"1rf1ag079569-01","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G2610077870","display_name":"Structure and Function of Gamma-Secretase in Familial Alzheimer's Disease","funder_award_id":"R01AG066986","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G3206710984","display_name":null,"funder_award_id":"RF1AG079569","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G3881021852","display_name":null,"funder_award_id":"AG79569","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G8883367568","display_name":null,"funder_award_id":"HEK293","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G8969343261","display_name":null,"funder_award_id":"AG66986","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G9000150948","display_name":null,"funder_award_id":"GM103418","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G9000864426","display_name":"Leveraging Heterogeneity in Autosomal Dominant AD to Elucidate Pathophysiology and Improve AD Biomarkers","funder_award_id":"R01AG079569","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G9000869322","display_name":"Kansas IDeA Network of Biomedical Research Excellence 5","funder_award_id":"P20GM103418","funder_id":"https://openalex.org/F4320337354","funder_display_name":"National Institute of General Medical Sciences"}],"funders":[{"id":"https://openalex.org/F4320308347","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337337","display_name":"National Institute on Aging","ror":"https://ror.org/049v75w11"},{"id":"https://openalex.org/F4320337354","display_name":"National Institute of General Medical Sciences","ror":"https://ror.org/04q48ey07"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4407369314.pdf","grobid_xml":"https://content.openalex.org/works/W4407369314.grobid-xml"},"referenced_works_count":46,"referenced_works":["https://openalex.org/W380069984","https://openalex.org/W1481249341","https://openalex.org/W1552188451","https://openalex.org/W1560202903","https://openalex.org/W1639521477","https://openalex.org/W2010117436","https://openalex.org/W2029516184","https://openalex.org/W2036288989","https://openalex.org/W2048111211","https://openalex.org/W2049665829","https://openalex.org/W2065663907","https://openalex.org/W2080225612","https://openalex.org/W2084972185","https://openalex.org/W2088989293","https://openalex.org/W2089710618","https://openalex.org/W2116964904","https://openalex.org/W2118330889","https://openalex.org/W2120304489","https://openalex.org/W2121316843","https://openalex.org/W2128084592","https://openalex.org/W2144417521","https://openalex.org/W2151889964","https://openalex.org/W2157405068","https://openalex.org/W2329336071","https://openalex.org/W2559911659","https://openalex.org/W2567716890","https://openalex.org/W2600872530","https://openalex.org/W2908723002","https://openalex.org/W3107788929","https://openalex.org/W3119714211","https://openalex.org/W3128527973","https://openalex.org/W3216557857","https://openalex.org/W4220983497","https://openalex.org/W4231640017","https://openalex.org/W4280526065","https://openalex.org/W4285132881","https://openalex.org/W4292547101","https://openalex.org/W4303986453","https://openalex.org/W4376614794","https://openalex.org/W4378219872","https://openalex.org/W4383823195","https://openalex.org/W4391800171","https://openalex.org/W4399053952","https://openalex.org/W4399394558","https://openalex.org/W4399771215","https://openalex.org/W4401055811"],"related_works":["https://openalex.org/W4411951393","https://openalex.org/W4391800171","https://openalex.org/W4386579685","https://openalex.org/W3119714211","https://openalex.org/W2795424618","https://openalex.org/W2150684193","https://openalex.org/W7119979216","https://openalex.org/W4407941091","https://openalex.org/W4320725274","https://openalex.org/W4319880458"],"abstract_inverted_index":{"Abstract":[0],"Missense":[1],"mutations":[2,76,141,182,227],"in":[3,66,77,83,86,110,149,161,167,173,196,203,215],"the":[4,29,35,200,208,242,247,253],"amyloid":[5,25,36],"precursor":[6],"protein":[7],"(APP)":[8],"and":[9,18,79,93,142,231,238],"presenilin-1":[10],"(PSEN1)":[11],"cause":[12,81],"early-onset":[13],"familial":[14],"Alzheimer\u2019s":[15],"disease":[16],"(FAD)":[17],"alter":[19],"proteolytic":[20,129],"production":[21],"of":[22,38,42,57,89,115,118,127,156,199,210,217,249],"secreted":[23],"38-to-43-residue":[24],"\u03b2-peptides":[26],"(A\u03b2)":[27],"by":[28,45,63,134],"PSEN1-containing":[30],"\u03b3-secretase":[31,46,99,135,186,233,250],"complex,":[32],"ostensibly":[33],"supporting":[34],"hypothesis":[37],"pathogenesis.":[39],"However,":[40,153],"proteolysis":[41,88,251],"APP":[43,78,90,132],"substrate":[44,91,133],"is":[47],"processive,":[48],"involving":[49],"initial":[50],"endoproteolysis":[51],"to":[52,184,229],"produce":[53],"long":[54],"A\u03b2":[55,119,218],"peptides":[56],"48":[58],"or":[59],"49":[60],"residues":[61],"followed":[62],"carboxypeptidase":[64],"trimming":[65,163,216],"mostly":[67],"tripeptide":[68],"increments.":[69],"We":[70],"recently":[71],"reported":[72],"evidence":[73,224],"that":[74,94,144,177,225],"FAD":[75,116,140,181,226],"PSEN1":[80,139,180],"deficiencies":[82,209],"early":[84],"steps":[85,164],"processive":[87],"C99":[92],"this":[95,211],"results":[96],"from":[97],"stalled":[98,105,185,230,243],"enzyme-substrate":[100,234],"and/or":[101,235],"enzyme-intermediate":[102,236],"complexes.":[103,188],"These":[104,220],"complexes":[106,237],"triggered":[107],"synaptic":[108],"degeneration":[109],"a":[111],"C.":[112],"elegans":[113],"model":[114],"independently":[117],"production.":[120],"Here":[121],"we":[122],"conducted":[123],"full":[124],"quantitative":[125],"analysis":[126],"all":[128,145,178],"events":[130],"on":[131],"with":[136,207,241],"six":[137,146,179],"additional":[138],"found":[143],"are":[147,239],"deficient":[148,160],"multiple":[150],"processing":[151],"steps.":[152],"only":[154,195,214],"one":[155],"these":[157],"(F386S)":[158],"was":[159],"certain":[162],"but":[165],"not":[166,202],"endoproteolysis.":[168],"Fluorescence":[169],"lifetime":[170],"imaging":[171],"microscopy":[172],"intact":[174],"cells":[175],"revealed":[176],"lead":[183,228],"enzyme-substrate/intermediate":[187],"The":[189],"F386S":[190],"mutation,":[191],"however,":[192],"does":[193],"so":[194],"A\u03b2-rich":[197],"regions":[198],"cells,":[201],"C99-rich":[204],"regions,":[205],"consistent":[206,240],"mutant":[212],"enzyme":[213],"intermediates.":[219],"findings":[221],"provide":[222],"further":[223],"stabilized":[232],"process":[244],"rather":[245],"than":[246],"products":[248],"as":[252],"pathogenic":[254],"trigger.":[255]},"counts_by_year":[{"year":2026,"cited_by_count":5},{"year":2025,"cited_by_count":3}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2025-02-12T00:00:00"}
