biostudies-literatureCarbonell FThe Canadian Institutes of Health ResearchLumosityNIBIB NIH HHSNIA NIH HHSJanssen Alzheimer Immunotherapy Research & DevelopmentAlzheimer's Drug Discovery FoundationCogstateIXICO Ltd.Eisai Inc.Meso Scale DiagnosticsGE HealthcareW81XWH-12-2-0012Eli Lilly and CompanyCereSpir, Inc.FujirebioTransition TherapeuticsNovartis Pharmaceuticals CorporationEuroImmunAraclon BiotechAlzheimer's AssociationNIH HHSJohnson & Johnson Pharmaceutical Research & Development LLCServier; Takeda Pharmaceutical CompanyElan Pharmaceuticals, Inc.Neurotrack TechnologiesAbbVieBioClinica, Inc.Department of DefenseBristol-Myers Squibb CompanyPiramal ImagingNeuroRx ResearchAlzheimer's Disease Neuroimaging InitiativeBiospective IncBiogene14625https://www.ebi.ac.uk/biostudies/studies/S-EPMC11848043biostudies-literatureUnknown21(2)<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Highlights</h4>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.Alzheimer's & dementia : the journal of the Alzheimer's AssociationTau-related reduction of glucose metabolism in mild cognitive impairment occurs independently of APOE ε4 genotype and is influenced by Aβ.PMC11848043U01 AG024904Alzheimer's Disease Neuroimaging InitiativeBedell BJMcNicoll CCarbonell FZijdenbos APfalseTau-related reduction of glucose metabolism in mild cognitive impairment occurs independently of APOE ε4 genotype and is influenced by Aβ.<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Highlights</h4>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.2025-01-01T00:00:00Z2025 Feb2025-04-22T18:47:35.703Z2025-04-06T02:37:49.311ZS-EPMC118480433998900710.1002/alz.14625