{"doi":"10.1101/2021.04.07.438832","title":"<i>APOE ε4</i> allele advances the age-dependent decline of amyloid β clearance in the human cortex","abstract":"Abstract Introduction Our previous study indicated that the pericapillary clearance of amyloid β (Aβ) declines with age in APOE 3/3 subjects. Here, we examine whether the APOE ε 4 allele has an impact on this age-related decline. Methods We examined 69 autopsy brains of APOE ε 3/ ε 4 or APOE ε 3/ ε 3 individuals (30-65 years) for the immunohistochemical localization of intracellular, extracellular, and pericapillary Aβ in the cerebral cortex. Results In APOE ε 3/ ε 4 individuals, the percentage of Aβ positive pericapillary spaces began to decrease (p=0.030), and the number of extracellular Aβ particles increased in the early 30s (p=0.0008). Those average values were significantly lower (p&lt;0.0001) and higher (p&lt;0.0001), respectively, compared to APOE ε 3/ ε 3 individuals. Discussion Our observations indicate that APOE ε 4 allele advances by one decade at the onset of age-related decline in Aβ glymphatic clearance. This finding supports early clinical intervention and stratification by APOE genotype to prevent Aβ deposition and AD progression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":223744,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353675,"name":"Yusuke Kageyama","orcid":"0000-0002-3382-9881","position":1,"is_corresponding":false},{"id":269723,"name":"Olga Pletniková","orcid":"0000-0001-6516-4944","position":2,"is_corresponding":false},{"id":825940,"name":"Gay Rudow","orcid":null,"position":3,"is_corresponding":false},{"id":254759,"name":"Yang An","orcid":"0000-0002-3312-7265","position":4,"is_corresponding":false},{"id":825941,"name":"Yumi Irie","orcid":null,"position":5,"is_corresponding":false},{"id":825556,"name":"Akiko Kita","orcid":"0000-0002-5174-6238","position":6,"is_corresponding":false},{"id":825557,"name":"Kunio Miki","orcid":"0000-0002-8381-0871","position":7,"is_corresponding":false},{"id":20492,"name":" Ling Li","orcid":"0000-0002-9245-7387","position":8,"is_corresponding":false},{"id":825942,"name":"Pamela Southall","orcid":null,"position":9,"is_corresponding":false},{"id":825558,"name":"Kazuhiro Irie","orcid":"0000-0001-7109-8568","position":10,"is_corresponding":false},{"id":107084,"name":"Juan C. Troncoso","orcid":"0000-0001-9553-6673","position":11,"is_corresponding":false},{"id":312443,"name":"Atsushi Saito","orcid":"0000-0001-5304-5286","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-18T23:54:14.760456Z","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":[]}