{"doi":"10.1002/alz.12364","title":"Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults","abstract":"Abstract Introduction Neurite orientation dispersion and density imaging (NODDI), a multi‐compartment diffusion‐weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. Methods Using neuroimaging (NODDI and T1‐weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ) 42 /Aβ 40 and phosphorylated tau (p‐tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. Results We observed a significant CSF Aβ 42 /Aβ 40 × p‐tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p‐tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p‐tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. Discussion NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.","journal":"Alzheimer s & Dementia","year":2021,"id":159623,"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":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8632,"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":291166,"name":"Jack F.V. Hunt","orcid":"0000-0002-5719-9028","position":1,"is_corresponding":false},{"id":406234,"name":"Nagesh Adluru","orcid":"0000-0001-8330-1770","position":2,"is_corresponding":false},{"id":670889,"name":"Yue Ma","orcid":"0000-0003-1362-3752","position":3,"is_corresponding":false},{"id":536174,"name":"Carol A. Van Hulle","orcid":"0000-0002-2288-8819","position":4,"is_corresponding":false},{"id":419484,"name":"Douglas Dean","orcid":"0000-0002-7057-1285","position":5,"is_corresponding":false},{"id":396750,"name":"Steven Kecskemeti","orcid":"0000-0003-3589-430X","position":6,"is_corresponding":false},{"id":289693,"name":"Nathaniel A. Chin","orcid":"0000-0001-8008-9356","position":7,"is_corresponding":false},{"id":289694,"name":"Cynthia M. Carlsson","orcid":"0000-0001-5743-1563","position":8,"is_corresponding":false},{"id":289695,"name":"Sanjay Asthana","orcid":"0000-0002-3998-4479","position":9,"is_corresponding":false},{"id":230038,"name":"Sterling C. Johnson","orcid":"0000-0002-8501-545X","position":10,"is_corresponding":false},{"id":671639,"name":"Gwendlyn Kollmorgen","orcid":null,"position":11,"is_corresponding":false},{"id":671640,"name":"Richard Batrla","orcid":null,"position":12,"is_corresponding":false},{"id":670890,"name":"Norbert Wild","orcid":"0000-0001-8828-2513","position":13,"is_corresponding":false},{"id":409714,"name":"Katharina Buck","orcid":"0009-0001-5452-4374","position":14,"is_corresponding":false},{"id":27601,"name":"Henrik Zetterberg","orcid":"0000-0003-3930-4354","position":15,"is_corresponding":false},{"id":396751,"name":"Andrew L. Alexander","orcid":"0000-0003-2695-768X","position":16,"is_corresponding":false},{"id":27600,"name":"Kaj Blennow","orcid":"0000-0002-1890-4193","position":17,"is_corresponding":false},{"id":291168,"name":"Barbara B. Bendlin","orcid":"0000-0002-0580-9875","position":18,"is_corresponding":false},{"id":670888,"name":"N. Vogt","orcid":"0000-0002-2334-1495","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:44:39.550981Z","pmid":"33984184","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":[]}