{"doi":"10.1002/alz.065859","title":"Familial Alzheimer’s Disease‐linked Swedish mutation impairs APP axonal transport","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>It is well‐established that most familial Alzheimer’s disease (AD) mutations alter processing of the amyloid precursor protein (APP) and perturb the balance between its proteolytic fragments. Considering different APP fragments play a role in its axonal transport, we here ask whether familial APP mutations impair axonal transport and homeostasis.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Stem cells‐derived human neurons were transduced with either APP<jats:sub>wt</jats:sub>_GFP or APP<jats:sub>swe</jats:sub>_tRFP. Time‐lapse movies were analyzed using tracking algorithms to describe axonal transport parameters. Immunocytochemistry was performed to assess APP localization. To evaluate the impact of APP<jats:sub>swe</jats:sub> on other cargoes we also studied axonal transport of Rab5 endosomes.</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>Proportions of movement, velocity, and distances of APP<jats:sub>swe</jats:sub> particles were decreased in anterograde direction compared to wt, while increased pauses and reversions were found. Accumulation of APP at the soma compared to neurite was found for APP mutant vs wt. Moreover, effect of APP<jats:sub>swe</jats:sub> resulted in the enlargement of Rab5 endosomes vs ctrl. Furthermore, to validate other effects of the APP mutant on Rab5, we studied its transport and found changes in some parameters compared with the ctrl.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This work shows that APP<jats:sub>swe</jats:sub> impairs axonal transport. The change found on anterograde transport of APP<jats:sub>swe</jats:sub>, goes in hand with its accumulation at the soma vs neurite. Moreover, our results suggest that the Swedish mutation affects other proteins linked with APP, as described for the early‐endosome protein, Rab5. In line with many studies conducted on APP, our data suggest once more the importance of understanding as many mechanisms as possible involved in the biology of this protein.</jats:p></jats:sec>","journal":"Alzheimer's &amp; Dementia","year":2023,"id":672425,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1756867,"name":"Neda Dragisic","orcid":null,"position":1,"is_corresponding":false},{"id":1756868,"name":"Pratiksha Bhat","orcid":null,"position":2,"is_corresponding":false},{"id":1756870,"name":"Victorio Martin Pozo Devoto","orcid":null,"position":3,"is_corresponding":false},{"id":393527,"name":"Gorazd B. Stokin","orcid":"0000-0001-8430-8755","position":4,"is_corresponding":false},{"id":1756866,"name":"Monica Feole","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Familial Alzheimer’s Disease‐linked Swedish mutation impairs APP axonal transport","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>It is well‐established that most familial Alzheimer’s disease (AD) mutations alter processing of the amyloid precursor protein (APP) and perturb the balance between its proteolytic fragments. Considering different APP fragments play a role in its axonal transport, we here ask whether familial APP mutations impair axonal transport and homeostasis.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Stem cells‐derived human neurons were transduced with either APP<jats:sub>wt</jats:sub>_GFP or APP<jats:sub>swe</jats:sub>_tRFP. Time‐lapse movies were analyzed using tracking algorithms to describe axonal transport parameters. Immunocytochemistry was performed to assess APP localization. To evaluate the impact of APP<jats:sub>swe</jats:sub> on other cargoes we also studied axonal transport of Rab5 endosomes.</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>Proportions of movement, velocity, and distances of APP<jats:sub>swe</jats:sub> particles were decreased in anterograde direction compared to wt, while increased pauses and reversions were found. Accumulation of APP at the soma compared to neurite was found for APP mutant vs wt. Moreover, effect of APP<jats:sub>swe</jats:sub> resulted in the enlargement of Rab5 endosomes vs ctrl. Furthermore, to validate other effects of the APP mutant on Rab5, we studied its transport and found changes in some parameters compared with the ctrl.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This work shows that APP<jats:sub>swe</jats:sub> impairs axonal transport. The change found on anterograde transport of APP<jats:sub>swe</jats:sub>, goes in hand with its accumulation at the soma vs neurite. Moreover, our results suggest that the Swedish mutation affects other proteins linked with APP, as described for the early‐endosome protein, Rab5. In line with many studies conducted on APP, our data suggest once more the importance of understanding as many mechanisms as possible involved in the biology of this protein.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":null,"pmcid":null,"openalex_id":"https://openalex.org/W4380877287","authors":[],"funders":[],"total_grants":0,"fwci":0.1429,"citation_percentile":0.4444347,"influential_citations":0,"citation_trend":[{"year":2024,"count":1}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/alz.065859","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/alz.065859","host_type":"publisher"},{"url":"https://alz-journals.onlinelibrary.wiley.com/doi/pdf/10.1002/alz.065859","host_type":"publisher"},{"url":"https://doi.org/10.1002/alz.065859","host_type":"journal"}],"fields_of_study":["Alzheimer's disease research and treatments","Cellular transport and secretion","Microtubule and mitosis dynamics"],"mesh_terms":[],"keywords":["Soma","Axoplasmic transport","Endosome","Amyloid precursor protein","Neurite","Immunocytochemistry","Axon","Mutant","Mutation","Cell biology","Neuroscience","Transport protein","Chemistry","Biology","Alzheimer's disease","Medicine","Gene","Internal medicine","Biochemistry","Endocrinology","Disease"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T09:04:10.793410Z","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,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}