Institute of Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
J Alzheimers Dis. 2013;35(2):363-71. doi: 10.3233/JAD-122359.
Numerous serum and plasma based biomarkers of systemic inflammation have been linked to both neuropsychiatric disorders and Alzheimer's disease (AD). The present study investigated the relationship of clinical biomarkers of cardiovascular risk (cholesterol, triglycerides, and homocysteine) and a panel of markers of systemic inflammation (CRP, TNF-α, IL1-ra, IL-7, IL-10, IL-15, IL-18) and microvascular pathology (ICAM-1, VCAM-1) to neuropsychiatric symptoms in a sample with mild AD. Biomarker data was analyzed on a sample of 194 diagnosed with mild to moderate probable AD. The sample was composed of 127 females and 67 males. The presence of neuropsychiatric symptoms was gathered from interview with caretakers/family members using the Neuropsychiatric Inventory. For the total sample, IL-15, VCAM (vascular adhesion molecule), and triglycerides were significantly and negatively related to number of neuropsychiatric symptoms, and total cholesterol and homocysteine were positively related and as a group accounted for 16.1% of the variance. When stratified by gender, different patterns of significant biomarkers were found with relationships more robust for males for both total symptoms and symptom clusters. A combination of biomarkers of systemic inflammation, microvascular pathology, and clinical biomarkers of cardiovascular risk can account for a significant portion of the variance in the occurrence of neuropsychiatric symptoms in AD supporting a vascular and inflammatory component of psychiatric disorders found in AD. Gender differences suggest distinct impact of specific risks with total cholesterol, a measure of cardiovascular risk, being the strongest marker for males and IL-15, a marker of inflammation, being the strongest for females.
大量基于血清和血浆的全身炎症生物标志物与神经精神障碍和阿尔茨海默病（AD）都有关联。本研究调查了心血管风险的临床生物标志物（胆固醇、甘油三酯和同型半胱氨酸）和全身炎症标志物（CRP、TNF-α、IL1-ra、IL-7、IL-10、IL-15、IL-18）以及微血管病理学标志物（ICAM-1、VCAM-1）与轻度 AD 样本中神经精神症状的关系。对 194 名轻度至中度可能患有 AD 的患者的样本进行了生物标志物数据分析。该样本由 127 名女性和 67 名男性组成。神经精神症状的存在是通过与护理人员/家庭成员进行访谈，使用神经精神疾病问卷收集的。对于总样本，IL-15、VCAM（血管细胞黏附分子）和甘油三酯与神经精神症状的数量呈显著负相关，总胆固醇和同型半胱氨酸呈正相关，两者共同解释了 16.1%的方差。按性别分层后，发现不同模式的显著生物标志物，男性的总症状和症状群的关系更为显著。全身炎症、微血管病理学和心血管风险的临床生物标志物的组合可以解释 AD 中神经精神症状发生的相当一部分变异，支持在 AD 中发现的精神障碍的血管和炎症成分。性别差异表明特定风险的影响不同，总胆固醇（心血管风险的衡量指标）是男性的最强标志物，而 IL-15（炎症标志物）是女性的最强标志物。
