Hall James R, Wiechmann April R, Johnson Leigh A, Edwards Melissa, Barber Robert C, Cunningham Rebecca, Singh Meharvan, O'Bryant Sid E
Institute of Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA Department of Psychiatry and Behavioral Health, University of North Texas Health Science Center, Fort Worth, TX, USA.
Institute of Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX, USA Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.
J Alzheimers Dis. 2014;40(4):887-96. doi: 10.3233/JAD-131724.
Research on the link between APOEε4 and neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) has been inconsistent. Previous work has shown a relationship between serum biomarkers of vascular risk and inflammation and NPS in AD. The current study investigated the impact of APOEε4 status on the relationship between biomarkers of cardiovascular risk, systemic inflammation, and NPS. The sample was drawn from the TARCC Longitudinal Research Cohort; the final sample of 190 consisted of 124 females and 66 males meeting the diagnostic criteria for mild to moderate AD. 115 individuals were APOEε4 carriers and 75 were non-carriers. Serum-based clinical biomarkers of vascular risk and biomarkers of inflammation related to AD were analyzed. NPS data was gathered from caretakers/family members using the Neuropsychiatric Inventory. The significant biomarkers differed for carriers and non-carriers with IL15 being a negative biomarker of total NPS accounting for 12% of the variance for carriers and IL18 and TNFα negative predictors for non-carriers (18% of variance). Patterns related to specific symptoms were similar. Stratification by gender revealed significant biomarkers of total NPS for female carriers were negative IL15 and IL1ra (18% of variance) and for female non-carriers were negative IL18 and positive homocysteine. Total cholesterol was a positive biomarker of total NPS for both male carriers (36% of variance) and non-carriers (negative TNFα and total cholesterol, 32% of variance). These findings suggest that dysregulation of inflammatory activity is related to NPS, that cholesterol is a significant factor in the occurrence of NPS, and that gender and APOE status need to be considered.
关于载脂蛋白Eε4（APOEε4）与阿尔茨海默病（AD）神经精神症状（NPS）之间联系的研究结果并不一致。此前的研究表明，血管风险和炎症的血清生物标志物与AD中的NPS之间存在关联。当前的研究调查了APOEε4状态对心血管风险生物标志物、全身炎症与NPS之间关系的影响。样本取自TARCC纵向研究队列；最终的190名样本由124名女性和66名男性组成，他们均符合轻度至中度AD的诊断标准。115名个体为APOEε4携带者，75名个体为非携带者。分析了基于血清的血管风险临床生物标志物以及与AD相关的炎症生物标志物。使用神经精神科问卷从照料者/家庭成员处收集NPS数据。携带者和非携带者的显著生物标志物有所不同，白细胞介素15（IL15）是总NPS的负性生物标志物，占携带者方差的12%，而白细胞介素18（IL18）和肿瘤坏死因子α（TNFα）是非携带者的负性预测因子（方差的18%）。与特定症状相关的模式相似。按性别分层显示，女性携带者总NPS的显著生物标志物为负性的IL15和白细胞介素1受体拮抗剂（IL1ra）（方差的18%），女性非携带者为负性的IL18和正性的同型半胱氨酸。总胆固醇是男性携带者（方差的36%）和非携带者（负性TNFα和总胆固醇，方差的32%）总NPS的正性生物标志物。这些发现表明，炎症活动失调与NPS相关，胆固醇是NPS发生的重要因素，并且需要考虑性别和APOE状态。
