Association between Tau protein deposition and brain metabolites:N-acetylaspartate and creatine as potential biomarkers for advanced Alzheimer's disease

LI Xiaoyuan; ZHANG Yiyue; GU Yucheng; CHEN Nihong; QIAN Xinyu; ZHANG Pengjun; HAO Jiaxin; WANG Feng

doi:10.12122/j.issn.1673-4254.2025.11.07

Abstract：Objective To investigate the associations between Tau protein deposition and brain biochemical metabolites detected by proton magnetic resonance spectroscopy(1H-MRS)in patients with advanced Alzheimer's disease(AD).Methods From April,2022 to December,2024,64 Tau-positive AD patients and 29 healthy individuals underwent 18F-APN-1607 PET/MR and simultaneously acquired multi-voxel 1H-MRS in the Department of Nuclear Medicine,Nanjing First Hospital.Visual analysis and voxel-based analysis of PET/MR data were performed to investigate the Tau protein deposition patterns in AD patients.Valid voxels within the 1H-MRS field of view were selected,and their standardized uptake value ratio(SUVr)in PET and metabolite levels of N-acetylaspartate(NAA),choline(Cho),creatine(Cr),NAA/Cr,and Cho/Cr were recorded.The Tau-positive(Tau+)voxels and Tau-negative(Tau-)voxels of the AD patients were compared for PET and 1H-MRS parameters,and the correlations between the metabolites and Tau PET SUVr within Tau+voxels were analyzed.Results Significant Tau protein deposition were observed in the AD patients,involving mainly the bilateral frontal lobes(30.07%),parietal lobes(29.96%),temporal lobes(21.07%),and occipital lobes(15.89%).A total of 1422 valid voxels in AD group(including 994 Tau+and 428 Tau-voxels)and 814 voxels in the control group were selected.The AD patients showed significantly decreased NAA level and increased SUVr compared with the control group(P<0.05).Subgroup analyses revealed that Tau+voxels had higher SUVr and lower Cr and Cho/Cr than Tau-voxels(P<0.05).Compared with the control group,Tau+voxels exhibited higher SUVr and lower Cr(P<0.05),while Tau-voxels showed lower NAA(P=0.004).No significant differences were found in Cho or NAA/Cr among the subgroups(P>0.05).Within Tau+voxels,NAA,Cho,and Cr were negatively correlated with SUVr(P<0.001).Conclusion The patients with progressive AD have significant Tau protein deposition in the brain,which is correlated with alterations in metabolite levels.Decreased NAA is more prominent in early or pre-tau deposition stages,while Cr changes is more significant in the regions with Tau protein deposition,suggesting the potential of NAA and Cr as biomarkers for Tau protein deposition in AD for disease monitoring and treatment evaluation.