Abstract：
BACKGROUND: We aimed to unravel the underlying pathophysiology of the neurodegeneration (N) markers neurogranin (Ng), neurofilament light (NfL), and hippocampal volume (HCV), in Alzheimer\'s disease (AD) using cerebrospinal fluid (CSF) proteomics.
METHODS: Individuals without dementia were classified as A+ (CSF amyloid beta [Aβ]42), T+ (CSF phosphorylated tau181), and N+ or N- based on Ng, NfL, or HCV separately. CSF proteomics were generated and compared between groups using analysis of covariance.
RESULTS: Only a few individuals were A+T+Ng-. A+T+Ng+ and A+T+NfL+ showed different proteomic profiles compared to A+T+Ng- and A+T+NfL-, respectively. Both Ng+ and NfL+ were associated with neuroplasticity, though in opposite directions. Compared to A+T+HCV-, A+T+HCV+ showed few proteomic changes, associated with oxidative stress.
CONCLUSIONS: Different N markers are associated with distinct neurodegenerative processes and should not be equated. N markers may differentially complement disease staging beyond amyloid and tau. Our findings suggest that Ng may not be an optimal N marker, given its low incongruency with tau pathophysiology.
CONCLUSIONS: In Alzheimer\'s disease, neurogranin (Ng)+, neurofilament light (NfL)+, and hippocampal volume (HCV)+ showed differential protein expression in cerebrospinal fluid. Ng+ and NfL+ were associated with neuroplasticity, although in opposite directions. HCV+ showed few proteomic changes, related to oxidative stress. Neurodegeneration (N) markers may differentially refine disease staging beyond amyloid and tau. Ng might not be an optimal N marker, as it relates more closely to tau.
METHODS: Individuals without dementia were classified as A+ (CSF amyloid beta [Aβ]42), T+ (CSF phosphorylated tau181), and N+ or N- based on Ng, NfL, or HCV separately. CSF proteomics were generated and compared between groups using analysis of covariance.
RESULTS: Only a few individuals were A+T+Ng-. A+T+Ng+ and A+T+NfL+ showed different proteomic profiles compared to A+T+Ng- and A+T+NfL-, respectively. Both Ng+ and NfL+ were associated with neuroplasticity, though in opposite directions. Compared to A+T+HCV-, A+T+HCV+ showed few proteomic changes, associated with oxidative stress.
CONCLUSIONS: Different N markers are associated with distinct neurodegenerative processes and should not be equated. N markers may differentially complement disease staging beyond amyloid and tau. Our findings suggest that Ng may not be an optimal N marker, given its low incongruency with tau pathophysiology.
CONCLUSIONS: In Alzheimer\'s disease, neurogranin (Ng)+, neurofilament light (NfL)+, and hippocampal volume (HCV)+ showed differential protein expression in cerebrospinal fluid. Ng+ and NfL+ were associated with neuroplasticity, although in opposite directions. HCV+ showed few proteomic changes, related to oxidative stress. Neurodegeneration (N) markers may differentially refine disease staging beyond amyloid and tau. Ng might not be an optimal N marker, as it relates more closely to tau.
摘要：
背景：我们旨在揭示神经变性（N）标记神经颗粒蛋白（Ng）的潜在病理生理学，神经丝光（NfL），和海马体积（HCV），在阿尔茨海默病（AD）中使用脑脊液（CSF）蛋白质组学。
方法：没有痴呆的个体被分类为A+（CSF淀粉样β[Aβ]42），T+（CSF磷酸化Tau181），和N+或N-基于Ng，NFL,或单独的HCV。产生CSF蛋白质组学并使用协方差分析在组之间进行比较。
结果：只有少数个体是A+T+Ng-。与A+T+Ng-和A+T+NfL-相比，A+T+Ng+和A+T+NfL-显示不同的蛋白质组图谱，分别。Ng+和NfL+都与神经可塑性相关，虽然在相反的方向。与A+T+HC-相比，A+T+HCV+显示很少的蛋白质组变化，与氧化应激有关。
结论：不同的N标记与不同的神经变性过程相关，不应等同。N标记物可以区别地补充淀粉样蛋白和tau蛋白以外的疾病分期。我们的发现表明，Ng可能不是最佳的N标记，鉴于其与tau病理生理学的不一致性低。
结论：在阿尔茨海默病中，神经颗粒素(Ng)+,神经丝光(NfL)+,和海马体积（HCV）在脑脊液中显示差异蛋白表达。Ng+和NfL+与神经可塑性相关,虽然方向相反。HCV+显示很少的蛋白质组变化，与氧化应激有关。神经变性（N）标记物可以区别地改善淀粉样蛋白和tau蛋白以外的疾病分期。Ng可能不是最佳的N标记，因为它与tau关系更密切。
方法：没有痴呆的个体被分类为A+（CSF淀粉样β[Aβ]42），T+（CSF磷酸化Tau181），和N+或N-基于Ng，NFL,或单独的HCV。产生CSF蛋白质组学并使用协方差分析在组之间进行比较。
结果：只有少数个体是A+T+Ng-。与A+T+Ng-和A+T+NfL-相比，A+T+Ng+和A+T+NfL-显示不同的蛋白质组图谱，分别。Ng+和NfL+都与神经可塑性相关，虽然在相反的方向。与A+T+HC-相比，A+T+HCV+显示很少的蛋白质组变化，与氧化应激有关。
结论：不同的N标记与不同的神经变性过程相关，不应等同。N标记物可以区别地补充淀粉样蛋白和tau蛋白以外的疾病分期。我们的发现表明，Ng可能不是最佳的N标记，鉴于其与tau病理生理学的不一致性低。
结论：在阿尔茨海默病中，神经颗粒素(Ng)+,神经丝光(NfL)+,和海马体积（HCV）在脑脊液中显示差异蛋白表达。Ng+和NfL+与神经可塑性相关,虽然方向相反。HCV+显示很少的蛋白质组变化，与氧化应激有关。神经变性（N）标记物可以区别地改善淀粉样蛋白和tau蛋白以外的疾病分期。Ng可能不是最佳的N标记，因为它与tau关系更密切。
