Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA.
Neurology. 2012 Mar 6;78(10):709-19. doi: 10.1212/WNL.0b013e318248e568. Epub 2012 Feb 22.
Measures of neuronal damage/dysfunction are likely good surrogates for disease progression in Alzheimer disease (AD). CSF markers of neuronal injury may offer utility in predicting disease progression and guiding prognostic and outcome assessments in therapeutic trials. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. We here investigate the utility of VILIP-1 and VILIP-1/Aβ42 in predicting rates of cognitive decline in early AD.
Individuals with a clinical diagnosis of very mild or mild AD (n = 60) and baseline CSF measures of VILIP-1, tau, p-tau181, and Aβ42 were followed longitudinally for an average of 2.6 years. Annual assessments included the Clinical Dementia Rating (CDR), CDR-sum of boxes (CDR-SB), and global composite scores. Mixed linear models assessed the ability of CSF biomarker measures to predict rates of cognitive decline over time.
Baseline CSF VILIP-1 and VILIP-1/Aβ42 levels predicted rates of future decline in CDR-SB and global composite scores over the follow-up period. Individuals with CSF VILIP-1 ≥560 pg/mL (corresponding to the upper tercile) progressed much more rapidly in CDR-SB (1.61 boxes/year; p = 0.0077) and global scores (-0.53 points/year; p = 0.0002) than individuals with lower values (0.85 boxes/year and -0.15 points/year, respectively) over the follow-up period. CSF tau, p-tau181, tau/Aβ42, and p-tau181/Aβ42 also predicted more rapid cognitive decline in CDR-SB and global scores over time.
These findings suggest that CSF VILIP-1 and VILIP-1/Aβ42 predict rates of global cognitive decline similarly to tau and tau/Aβ42, and may be useful CSF surrogates for neurodegeneration in early AD.
神经元损伤/功能障碍的测量可能是阿尔茨海默病（AD）疾病进展的良好替代指标。神经元损伤的 CSF 标志物可能有助于预测疾病进展，并指导治疗试验中的预后和结局评估。类视黄醇蛋白-1（VILIP-1）已被证明具有作为神经元损伤标志物的潜力。我们在此研究 VILIP-1 和 VILIP-1/Aβ42 预测早期 AD 认知下降速度的效用。
60 名临床诊断为轻度或轻度 AD 的个体具有基线 CSF 水平的 VILIP-1、tau、p-tau181 和 Aβ42，平均随访 2.6 年。每年评估包括临床痴呆评分（CDR）、CDR 总盒数（CDR-SB）和全球综合评分。混合线性模型评估 CSF 生物标志物测量值预测随时间发生认知下降速度的能力。
基线 CSF VILIP-1 和 VILIP-1/Aβ42 水平预测了随访期间 CDR-SB 和全球综合评分的未来下降速度。CSF VILIP-1≥560pg/mL（对应上三分位数）的个体在 CDR-SB（1.61 个框/年；p=0.0077）和全球评分（-0.53 分/年；p=0.0002）方面的进展速度明显快于低值（0.85 个框/年和-0.15 分/年，分别）在随访期间。CSF tau、p-tau181、tau/Aβ42 和 p-tau181/Aβ42 也随时间预测了 CDR-SB 和全球评分的认知下降速度更快。
这些发现表明，CSF VILIP-1 和 VILIP-1/Aβ42 与 tau 和 tau/Aβ42 相似，可预测 AD 早期的全球认知下降速度，可能是神经元退行性变的有用 CSF 替代指标。
