Abstract：
BACKGROUND: Neuronal pentraxin-2 (NPTX2), crucial for synaptic functioning, declines in cerebrospinal fluid (CSF) as cognition deteriorates. The variations of CSF NPTX2 across mild cognitive impairment (MCI) due to Alzheimer\'s disease (AD) and its association with brain metabolism remain elusive, albeit relevant for patient stratification and pathophysiological insights.
METHODS: We retrospectively analyzed 49 MCI-AD patients grouped by time until dementia (EMCI, n = 34 progressing within 2 years; LMCI, n = 15 progressing later/stable at follow-up). We analyzed demographic variables, cognitive status (MMSE score), and CSF NPTX2 levels using a commercial ELISA assay in EMCI, LMCI, and a control group of age-/sex-matched individuals with other non-dementing disorders (OND). Using [18F]FDG PET scans for voxel-based analysis, we explored correlations between regional brain metabolism metrics and CSF NPTX2 levels in MCI-AD patients, accounting for age.
RESULTS: Baseline and follow-up MMSE scores were lower in LMCI than EMCI (p value = 0.006 and p < 0.001). EMCI exhibited significantly higher CSF NPTX2 values than both LMCI (p = 0.028) and OND (p = 0.006). We found a significant positive correlation between NPTX2 values and metabolism of bilateral precuneus in MCI-AD patients (p < 0.005 at voxel level, p < 0.05 with family-wise error correction at the cluster level).
CONCLUSIONS: Higher CSF NPTX2 in EMCI compared to controls and LMCI suggests compensatory synaptic responses to initial AD pathology. Disease progression sees these mechanisms overwhelmed, lowering CSF NPTX2 approaching dementia. Positive CSF NPTX2 correlation with precuneus glucose metabolism links to AD-related metabolic changes across MCI course. These findings posit CSF NPTX2 as a promising biomarker for both AD staging and progression risk stratification.
METHODS: We retrospectively analyzed 49 MCI-AD patients grouped by time until dementia (EMCI, n = 34 progressing within 2 years; LMCI, n = 15 progressing later/stable at follow-up). We analyzed demographic variables, cognitive status (MMSE score), and CSF NPTX2 levels using a commercial ELISA assay in EMCI, LMCI, and a control group of age-/sex-matched individuals with other non-dementing disorders (OND). Using [18F]FDG PET scans for voxel-based analysis, we explored correlations between regional brain metabolism metrics and CSF NPTX2 levels in MCI-AD patients, accounting for age.
RESULTS: Baseline and follow-up MMSE scores were lower in LMCI than EMCI (p value = 0.006 and p < 0.001). EMCI exhibited significantly higher CSF NPTX2 values than both LMCI (p = 0.028) and OND (p = 0.006). We found a significant positive correlation between NPTX2 values and metabolism of bilateral precuneus in MCI-AD patients (p < 0.005 at voxel level, p < 0.05 with family-wise error correction at the cluster level).
CONCLUSIONS: Higher CSF NPTX2 in EMCI compared to controls and LMCI suggests compensatory synaptic responses to initial AD pathology. Disease progression sees these mechanisms overwhelmed, lowering CSF NPTX2 approaching dementia. Positive CSF NPTX2 correlation with precuneus glucose metabolism links to AD-related metabolic changes across MCI course. These findings posit CSF NPTX2 as a promising biomarker for both AD staging and progression risk stratification.
摘要：
背景：神经元pentraxin-2（NPTX2），对突触功能至关重要，随着认知能力的恶化，脑脊液（CSF）下降。由于阿尔茨海默病（AD）引起的轻度认知障碍（MCI）的CSFNPTX2的变化及其与脑代谢的关联仍然难以捉摸，尽管与患者分层和病理生理学见解有关。
方法：我们回顾性分析了49例MCI-AD患者，按痴呆时间分组（EMCI，n=34，2年内进展；LMCI，n=15进展较晚/随访稳定）。我们分析了人口统计变量，认知状态（MMSE评分），在EMCI，LMCI和具有其他非痴呆性疾病（OND）的年龄/性别匹配个体的对照组中使用商业ELISA测定和CSFNPTX2水平。使用[18F]FDGPET扫描进行基于体素的分析，我们探讨了MCI-AD患者局部脑代谢指标与CSFNPTX2水平之间的相关性，占年龄。
结果：LMCI的基线和随访MMSE评分低于EMCI（p值=0.006和p<0.001）。EMCI表现出显著高于LMCI(p=0.028)和OND(p=0.006)的CSFNPTX2值。我们发现MCI-AD患者的NPTX2值与双侧前肌代谢之间存在显着正相关（在体素水平，p<0.005，p<0.05，在集群级别进行家族错误校正)。
结论：与对照组和LMCI相比，EMCI中CSFNPTX2较高提示对初始AD病理的代偿性突触反应。疾病进展看到这些机制不堪重负，降低CSFNPTX2接近痴呆。CSFNPTX2与前期葡萄糖代谢的正相关性与整个MCI病程中AD相关的代谢变化有关。这些发现认为CSFNPTX2是AD分期和进展风险分层的有希望的生物标志物。
方法：我们回顾性分析了49例MCI-AD患者，按痴呆时间分组（EMCI，n=34，2年内进展；LMCI，n=15进展较晚/随访稳定）。我们分析了人口统计变量，认知状态（MMSE评分），在EMCI，LMCI和具有其他非痴呆性疾病（OND）的年龄/性别匹配个体的对照组中使用商业ELISA测定和CSFNPTX2水平。使用[18F]FDGPET扫描进行基于体素的分析，我们探讨了MCI-AD患者局部脑代谢指标与CSFNPTX2水平之间的相关性，占年龄。
结果：LMCI的基线和随访MMSE评分低于EMCI（p值=0.006和p<0.001）。EMCI表现出显著高于LMCI(p=0.028)和OND(p=0.006)的CSFNPTX2值。我们发现MCI-AD患者的NPTX2值与双侧前肌代谢之间存在显着正相关（在体素水平，p<0.005，p<0.05，在集群级别进行家族错误校正)。
结论：与对照组和LMCI相比，EMCI中CSFNPTX2较高提示对初始AD病理的代偿性突触反应。疾病进展看到这些机制不堪重负，降低CSFNPTX2接近痴呆。CSFNPTX2与前期葡萄糖代谢的正相关性与整个MCI病程中AD相关的代谢变化有关。这些发现认为CSFNPTX2是AD分期和进展风险分层的有希望的生物标志物。
