Tau蛋白沉积与脑代谢物的关联性：N-乙酰天门冬氨酸与肌酸作为进展期阿尔茨海默病的潜在生物标志物

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Abstract：ObjectiveToinvestigate theassociationsbetweenTauproteindepositionandbrainbiochemicalmetabolites detected by proton magneticresonance spectroscopy（H-MRS）inpatients with advanced Alzheimer's disease （AD）.Methods FromApril，2022 to December，2024，64 Tau-positive ADpatientsand29healthyindividualsunderwent 18F -APN-1607PET/MR and simultaneously acquired multi-voxel 1H -MRSin the DepartmentofNuclearMedicine，Nanjing FirstHospital.Visual analysisandvoxel-basedanalysisofPET/MRdatawereperformedtoinvestigatetheTauproteindepositionpaternsinAD patients. Valid voxelswithin the 1H -MRS field of viewwere selected，and their standardized uptake value ratio （SUVr） in PET andmetabolite levelsof N-acetylaspartate （NAA），choline （Cho），creatine （Cr） ，NAA/Cr，ad Cho/Cr wererecorded. The Taupositive （Tau*） voxels and Tau-negative （Tau）voxels of theAD patients were compared for PETand 1H -MRSparameters，and thecorrelationsbetweenthemetabolitesandTauPETSUVrwithinTau+voxelswereanalyzed.Results SignificantTauprotein depositionwereobserved intheAD patients，involvingmainlythebilateral frontal lobes （30.07% ），parietallobes （29.96% ） temporal lobes （21.07% ），andoccipitallobes （15.89% ）.Atotalof1422validvoxelsinADgroup （including 994Tau+ and 428Tau voxels）and814 voxels inthecontrol group were selected.The ADpatients showed significantly decreasedNAAleveland increased SUVr compared with the control group （P<0.05） .SubgroupanalysesrevealedthatTau+voxelshad higher SUVr and lower Crand Cho/Cr than Tauvoxels （P<0.05） . Compared with the control group， Tau+ voxels exhibited higher SUVrand lower while Tau voxelsshowed lower NAA （P=0.004） . No significant differences were found in Cho or NAA/Cr among the subgroups （P>0.05） .Withinxels，A， Cr werenegativelycorrelated with SUVr （P<0.001） .Conclusion ThepatientswithprogressiveADavesignificantTauproteindepositioninthebrain，whichiscorelatedwithalerationsin metabolite levels. Decreased NAA is more prominent in earlyor pre-tau deposition stages， while Cr changes is more significantintheregionswith Tauproteindeposition， suggestingthepotentialofNAAandCrasbiomarkersfor Tauprotein deposition inAD for diseasemonitoringand treatmentevaluation.

Keywords： Alzheimer'sdisease; positron emission tomography/magneticresonance imaging;Tau protein; 18F-APN-1607; N-acetylaspartate

阿尔茨海默病（AD）是一种以认知功能障碍为特征的神经系统退行性疾病，其核心病理标志包括β淀粉样蛋白（Aβ）沉积和Tau蛋白异常磷酸化形成的神经原纤维缠结（NFTs）[2。（剩余14849字）