{"doi":"10.1002/alz.14625","title":"Tau‐related reduction of glucose metabolism in mild cognitive impairment occurs independently of <i>APOE</i> ε4 genotype and is influenced by Aβ","abstract":"INTRODUCTION: Positron emission tomography (PET) imaging studies have shown that amyloid beta (Aβ) is significantly correlated with glucose metabolism in mild cognitive impairment independently of the apolipoprotein E (APOE) ε4 genotype. METHODS: We used a singular value decomposition (SVD) approach to pairwise cross-correlation among tau, Aβ, and fluorodeoxyglucose PET images. The resulting SVD-based tau and Aβ scores as well as the APOE ε4 genotype, were entered as predictors in a voxelwise general linear model for statistical assessment of their effect on FDG. RESULTS: We found cortical regions where a reduced glucose metabolism was maximally correlated with distributed patterns of tau, accounting for the effect of Aβ and APOE ε4 genotype. DISCUSSION: By highlighting the more significant role of tau, rather than Aβ, in the reduction of glucose metabolism, our results provide a better understanding of their combined effect in the development and progression of Alzheimer's disease. HIGHLIGHTS: This study uses a data-driven singular value decomposition approach to the cross-correlation matrix between tau and fluorodeoxyglucose (FDG) images, as well as between FDG and amyloid beta (Aβ) positron emission tomography (PET) images. From a population of mild cognitive impairment subjects, we found that spatially distributed scores of tau PET are associated with an even stronger reduction of glucose metabolism, independent of the apolipoprotein E ε4 genotype and confounded by Aβ. By highlighting the more significant role of tau, rather than Aβ, on the reduction of glucose metabolism, our results provide a better understanding of their combined effects in the development of Alzheimer's disease.","journal":"Alzheimer s & Dementia","year":2025,"id":520633,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9633,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1192944,"name":"Carolann McNicoll","orcid":null,"position":1,"is_corresponding":false},{"id":600678,"name":"Alex Zijdenbos","orcid":null,"position":2,"is_corresponding":false},{"id":1192945,"name":"Barry J. Bedell","orcid":null,"position":3,"is_corresponding":false},{"id":300139,"name":"for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":4,"is_corresponding":false},{"id":656989,"name":"Félix Carbonell","orcid":"0000-0002-1450-0423","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:49:28.470782Z","pmid":"39989007","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":[]}