| Summary: | Alzheimer’s disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (<sup>1</sup>H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (<i>p</i> = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with <i>p</i> < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (<i>r</i> = −0.47, <i>p</i> < 0.001) and tau load (<i>r</i> = −0.51, <i>p</i> < 0.001) and allowed a discrimination of early AD from controls (<i>p</i> < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD.
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