{"doi":"10.1126/science.8191290","title":"An Increased Percentage of Long Amyloid β Protein Secreted by Familial Amyloid β Protein Precursor (βApp\n            <sub>717</sub>\n            ) Mutants","abstract":"<jats:p>\n            Normal processing of the amyloid β protein precursor (βAPP) results in secretion of a soluble 4-kilodalton protein essentially identical to the amyloid β protein (Aβ) that forms insoluble fibrillar deposits in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing wild-type βAPP or the βAPP\n            <jats:sub>717</jats:sub>\n            mutants linked to familial Alzheimer's disease were compared by (i) isolation of metabolically labeled 4-kilodalton Aβ from conditioned medium, digestion with cyanogen bromide, and analysis of the carboxyl-terminal peptides released, or (ii) analysis of the Aβ in conditioned medium with sandwich enzyme-linked immunosorbent assays that discriminate Aβ\n            <jats:sub>1-40</jats:sub>\n            from the longer Aβ\n            <jats:sub>1-42</jats:sub>\n            . Both methods demonstrated that the 4-kilodalton Aβ released from wild-type βAPP is primarily but not exclusively Aβ\n            <jats:sub>1-40</jats:sub>\n            . The βAPP\n            <jats:sub>717</jats:sub>\n            mutations, which are located three residues carboxyl to Aβ\n            <jats:sub>43</jats:sub>\n            , consistently caused a 1.5- to 1.9-fold increase in the percentage of longer Aβ generated. Long Aβ (for example, Aβ\n            <jats:sub>1-42</jats:sub>\n            ) forms insoluble amyloid fibrils more rapidly than Aβ\n            <jats:sub>1-40</jats:sub>\n            . Thus, the βAPP\n            <jats:sub>717</jats:sub>\n            mutants may cause Alzheimer's disease because they secrete increased amounts of long Aβ, thereby fostering amyloid deposition.\n          </jats:p>","journal":"Science","year":1994,"id":26855,"datarank":19.683629649566228,"base_score":7.293017679772782,"endowment":7.293017679772782,"self_citation_contribution":1.0939526519659175,"citation_network_contribution":18.58967699760031,"self_endowment_contribution":1.0939526519659175,"citer_contribution":18.58967699760031,"corpus_percentile":null,"corpus_rank":null,"citation_count":1469,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":154367,"name":"Tobun T. Cheung","orcid":null,"position":1,"is_corresponding":false},{"id":154368,"name":"Xiao-Dan Cai","orcid":null,"position":2,"is_corresponding":false},{"id":154369,"name":"Asano Odaka","orcid":null,"position":3,"is_corresponding":false},{"id":118692,"name":"Laszlo Otvos","orcid":null,"position":4,"is_corresponding":false},{"id":154370,"name":"Christopher Eckman","orcid":null,"position":5,"is_corresponding":false},{"id":107091,"name":"Todd E. Golde","orcid":"0000-0003-1867-7071","position":6,"is_corresponding":false},{"id":775,"name":"Steven G. Younkin","orcid":null,"position":7,"is_corresponding":false},{"id":154366,"name":"Nobuhiro Suzuki","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":7.293017679772782,"endowment":7.293017679772782,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"8191290","pmcid":null,"openalex_id":"https://openalex.org/W1980906872","authors":[],"funders":[{"funder_name":"NIA NIH HHS","grant_id":"AG06656","title":null}],"total_grants":1,"fwci":55.9353,"citation_percentile":0.99974339,"influential_citations":42,"citation_trend":[{"year":2012,"count":45},{"year":2013,"count":33},{"year":2014,"count":28},{"year":2015,"count":27},{"year":2016,"count":23},{"year":2017,"count":26},{"year":2018,"count":26},{"year":2019,"count":23},{"year":2020,"count":28},{"year":2021,"count":12},{"year":2022,"count":30},{"year":2023,"count":17},{"year":2024,"count":22},{"year":2025,"count":18},{"year":2026,"count":6}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/science.8191290","host_type":"publisher"},{"url":"https://doi.org/10.1126/science.8191290","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8191290","host_type":"repository"}],"fields_of_study":["Alzheimer's disease research and treatments","Amyloidosis: Diagnosis, Treatment, Outcomes","Prion Diseases and Protein Misfolding","Biology","Medicine","Alzheimer Disease","Amyloid beta-Peptides","Amyloid beta-Protein Precursor","Culture Media, Conditioned","Enzyme-Linked Immunosorbent Assay","Humans","Mutation","Neuroblastoma","Transfection","Tumor Cells, Cultured"],"mesh_terms":["Alzheimer Disease","Enzyme-Linked Immunosorbent Assay","Humans","Mutation","Neuroblastoma","Transfection","Tumor Cells, Cultured","Amyloid beta-Peptides","Amyloid beta-Protein Precursor","Culture Media, Conditioned"],"keywords":["BETA (programming language)","Cyanogen bromide","Amyloid precursor protein","Amyloid beta","Protein precursor","Amyloid (mycology)","Mutant","Chemistry","Secretion","Biochemistry of Alzheimer's disease","Molecular biology","Biochemistry","BACE1-AS","Amyloid precursor protein secretase","Alzheimer's disease","Biology","Peptide","Enzyme","Peptide sequence","Internal medicine","Gene","Medicine","Disease"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.13346572.v1","title":"Additional file 1 of Collagenous Alzheimer amyloid plaque component impacts on the compaction of amyloid-β plaques","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.13346572","title":"Additional file 1 of Collagenous Alzheimer amyloid plaque component impacts on the compaction of amyloid-β plaques","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T15:52:09.887499Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}