{"doi":"10.1093/cercor/bhac239","title":"Genotypic effects of<i>APOE</i>-ε4 on resting-state connectivity in cognitively intact individuals support functional brain compensation","abstract":"The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer's disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-ε4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carriers of the ε4 allele. Yet, no study has assessed APOE-ε4 gene-dose effects on rsFC measures, and only a few studies included measures of cognitive performance to aid a clinical interpretation. We assessed the impact of APOE-ε4 on rsFC in a sample of 429 cognitively unimpaired individuals hosting a high number of ε4 homozygotes (n = 58), which enabled testing different models of genetic penetrance. We used independent component analysis and found a reduced rsFC as a function of the APOE-ε4 allelic load in the temporal default-mode and the medial temporal networks, while recessive effects were found in the extrastriate and limbic networks. Some of these results were replicated in a subsample with negative amyloid markers. Interaction with cognitive data suggests that such a network reorganization may support cognitive performance in the ε4-homozygotes. Our data indicate that APOE-ε4 shapes the functional architecture of the resting brain and favor the idea of a network-based functional compensation.","journal":"Cerebral Cortex","year":2022,"id":257621,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":872710,"name":"Grégory Operto","orcid":"0000-0002-0208-1671","position":1,"is_corresponding":false},{"id":872711,"name":"Carles Falcón","orcid":"0000-0001-5564-2025","position":2,"is_corresponding":false},{"id":908621,"name":"José Maria González de Echavarri-Gómez","orcid":null,"position":3,"is_corresponding":false},{"id":654908,"name":"Gonzalo Sánchez‐Benavides","orcid":"0000-0003-3454-800X","position":4,"is_corresponding":false},{"id":843595,"name":"Anna Brugulat‐Serrat","orcid":"0000-0001-8988-5658","position":5,"is_corresponding":false},{"id":658015,"name":"Marta Milà‐Alomà","orcid":"0000-0002-5687-4597","position":6,"is_corresponding":false},{"id":27600,"name":"Kaj Blennow","orcid":"0000-0002-1890-4193","position":7,"is_corresponding":false},{"id":27601,"name":"Henrik Zetterberg","orcid":"0000-0003-3930-4354","position":8,"is_corresponding":false},{"id":27626,"name":"José Luís Molinuevo","orcid":"0000-0003-0485-6001","position":9,"is_corresponding":false},{"id":241108,"name":"Marc Suárez‐Calvet","orcid":"0000-0002-2993-569X","position":10,"is_corresponding":false},{"id":518200,"name":"Juan Domingo Gispert","orcid":"0000-0002-6155-0642","position":11,"is_corresponding":false},{"id":874623,"name":"for the ALFA study","orcid":null,"position":12,"is_corresponding":false},{"id":874235,"name":"Müge Akinci","orcid":"0000-0002-0845-933X","position":13,"is_corresponding":false},{"id":67225,"name":"Annabella Beteta","orcid":null,"position":14,"is_corresponding":false},{"id":874236,"name":"Alba Cañas","orcid":"0000-0001-5664-6941","position":15,"is_corresponding":false},{"id":874624,"name":"Irene Cumplido","orcid":null,"position":16,"is_corresponding":false},{"id":874625,"name":"Carme Deulofeu","orcid":null,"position":17,"is_corresponding":false},{"id":874626,"name":"Ruth Dominguez","orcid":null,"position":18,"is_corresponding":false},{"id":874627,"name":"Maria Emilio","orcid":null,"position":19,"is_corresponding":false},{"id":839826,"name":"Karine Fauria","orcid":"0000-0003-1506-4405","position":20,"is_corresponding":false},{"id":874628,"name":"Sherezade Fuentes","orcid":null,"position":21,"is_corresponding":false},{"id":842008,"name":"Oriol Grau‐Rivera","orcid":"0000-0002-4730-5341","position":22,"is_corresponding":false},{"id":385813,"name":"Laura L. 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