Buchhave Peder, Minthon Lennart, Zetterberg Henrik, Wallin Asa K, Blennow Kaj, Hansson Oskar
Neuropsychiatric Clinic, Skåne University Hospital, Malmö, Sweden.
Arch Gen Psychiatry. 2012 Jan;69(1):98-106. doi: 10.1001/archgenpsychiatry.2011.155.
Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease.
To assess the ability of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42) to predict future development of AD dementia within 9.2 years in patients with mild cognitive impairment (MCI) and to compare CSF biomarkers between early and late converters to AD.
A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years).
Memory disorder clinic. Patients A total of 137 patients with MCI who underwent lumbar puncture at baseline. MAIN OUTCOME MEASURE Conversion to AD dementia.
During follow-up, 72 patients (53.7%) developed AD and 21 (15.7%) progressed to other forms of dementia. At baseline, CSF Aβ42 levels were reduced and T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with nonconverters (P < .001). Baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted to AD within 0 to 5 years (early converters) compared with those who converted between 5 and 10 years (late converters). However, CSF T-tau and P-tau levels were significantly higher in early converters vs late converters. A baseline Aβ42:P-tau ratio predicted the development of AD within 9.2 years with a sensitivity of 88%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 86%.
Approximately 90% of patients with MCI and pathologic CSF biomarker levels at baseline develop AD within 9 to 10 years. Levels of Aβ42 are already fully decreased at least 5 to 10 years before conversion to AD dementia, whereas T-tau and P-tau seem to be later markers. These results provide direct support in humans for the hypothesis that altered Aβ metabolism precedes tau-related pathology and neuronal degeneration.
前驱性阿尔茨海默病（AD）的早期检测很重要，因为新的疾病修饰疗法在疾病早期启动时最有可能有效。
评估脑脊液（CSF）生物标志物总tau蛋白（T-tau）、磷酸化tau蛋白（P-tau）和β淀粉样蛋白1-42（Aβ42）预测轻度认知障碍（MCI）患者在9.2年内未来发生AD痴呆的能力，并比较早期和晚期进展为AD的患者之间的CSF生物标志物。
一项中位随访时间为9.2年（范围4.1 - 11.8年）的临床研究。
记忆障碍诊所。患者共有137例在基线时接受腰椎穿刺的MCI患者。主要观察指标进展为AD痴呆。
随访期间，72例患者（53.7%）发生AD，21例（15.7%）进展为其他形式的痴呆。在基线时，与未进展者相比，随访期间进展为AD的患者CSF Aβ42水平降低，T-tau和P-tau水平升高（P <.001）。在0至5年内进展为AD的MCI患者（早期进展者）与在5至10年内进展为AD的患者（晚期进展者）相比，基线CSF Aβ42水平同样降低。然而，早期进展者的CSF T-tau和P-tau水平显著高于晚期进展者。基线Aβ42:P-tau比值预测9.2年内AD发生的敏感性为88%，特异性为90%，阳性预测值为91%，阴性预测值为86%。
约90%基线时CSF生物标志物水平异常的MCI患者在9至10年内发生AD。在进展为AD痴呆前至少5至10年，Aβ42水平已完全降低，而T-tau和P-tau似乎是较晚出现变化的标志物。这些结果在人体中为Aβ代谢改变先于tau相关病理和神经元变性这一假说提供了直接支持。
