{"doi":"10.1007/s00259-021-05192-8","title":"Differential associations of APOE-ε2 and APOE-ε4 alleles with PET-measured amyloid-β and tau deposition in older individuals without dementia","abstract":"Abstract Purpose To examine associations between the APOE-ε2 and APOE-ε4 alleles and core Alzheimer’s disease (AD) pathological hallmarks as measured by amyloid-β (Aβ) and tau PET in older individuals without dementia. Methods We analyzed data from 462 ADNI participants without dementia who underwent Aβ ([ 18 F]florbetapir or [ 18 F]florbetaben) and tau ([ 18 F]flortaucipir) PET, structural MRI, and cognitive testing. Employing APOE-ε3 homozygotes as the reference group, associations between APOE-ε2 and APOE-ε4 carriership with global Aβ PET and regional tau PET measures (entorhinal cortex (ERC), inferior temporal cortex, and Braak-V/VI neocortical composite regions) were investigated using linear regression models. In a subset of 156 participants, we also investigated associations between APOE genotype and regional tau accumulation over time using linear mixed models. Finally, we assessed whether Aβ mediated the cross-sectional and longitudinal associations between APOE genotype and tau. Results Compared to APOE-ε3 homozygotes, APOE-ε2 carriers had lower global Aβ burden (β std [95% confidence interval (CI)]: − 0.31 [− 0.45, − 0.16], p = 0.034) but did not differ on regional tau burden or tau accumulation over time . APOE-ε4 participants showed higher Aβ (β std [95%CI]: 0.64 [0.42, 0.82], p < 0.001) and tau burden (β std range: 0.27-0.51, all p < 0.006). In mediation analyses, APOE-ε4 only retained an Aβ-independent effect on tau in the ERC. APOE-ε4 showed a trend towards increased tau accumulation over time in Braak-V/VI compared to APOE-ε3 homozygotes (β std [95%CI]: 0.10 [− 0.02, 0.18], p = 0.11), and this association was fully mediated by baseline Aβ. Conclusion Our data suggest that the established protective effect of the APOE-ε2 allele against developing clinical AD is primarily linked to resistance against Aβ deposition rather than tau pathology.","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2021,"id":161971,"datarank":0.5955437870328184,"base_score":3.970291913552122,"endowment":3.970291913552122,"self_citation_contribution":0.5955437870328184,"citation_network_contribution":0.0,"self_endowment_contribution":0.5955437870328184,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9368,"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":241103,"name":"Michel J. Grothe","orcid":"0000-0003-2600-9022","position":1,"is_corresponding":false},{"id":332619,"name":"Colin Groot","orcid":"0000-0002-5802-6946","position":2,"is_corresponding":false},{"id":241102,"name":"Alexis Moscoso","orcid":"0000-0003-0170-036X","position":3,"is_corresponding":false},{"id":241109,"name":"Michael Schöll","orcid":"0000-0001-7800-1781","position":4,"is_corresponding":false},{"id":518200,"name":"Juan Domingo Gispert","orcid":"0000-0002-6155-0642","position":5,"is_corresponding":false},{"id":230944,"name":"Rik Ossenkoppele","orcid":"0000-0003-1584-7477","position":6,"is_corresponding":false},{"id":243718,"name":"for the Alzheimer’s Disease Neuroimaging Initiative","orcid":null,"position":7,"is_corresponding":false},{"id":658019,"name":"Gemma Salvadó","orcid":"0000-0002-5210-9230","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:45:00.600065Z","pmid":"33521872","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":[]}