2012年1月2日，据《每日科学》报道，在患轻度认知功能损害的患者发展为阿尔兹海默病（AD）痴呆症之前，其脑脊液中Aβ42的水平似乎已经下降了至少5至10年，而其他的一些因子的脑脊液水平似乎是AD的迟发性标记物，根据1月期的Archives of General Psychiatry期刊（JAMA/Archives期刊的一种）上的一则研究报告。
研究人员指出，如果能够在疾病的早期阶段应用疾病修饰疗法如免疫治疗，则更有可能成功。
因此有必要在神经退行性病症发展不是太严重之前鉴定出阿尔茨海默病患者。
Peder Buchhave，医学博士，任职于瑞士隆德大学和斯科纳大学，和同事们对以前的一个137例患轻度认知功能障碍（MCI）的研究进行了一个扩展的随访队列研究，平均随访时间为9.2年。
在跟进随访中，72例（53.7%）患上了阿尔兹海默病（AD），21例（15.7%）发展成了其他形式的老年痴呆症。在基线水平，与没有发展为AD的患者相比，发展为AD的患者其脑脊液中，Aβ42水平降低了而其他生物标志物如T-tau和P-tau蛋白水平升高了。
研究表明，与那些在5-10年内转变为AD 的MCI患者相比，在5年内转变为AD的MCI患者中脑脊液Aβ42基线水平同等的减少了。
研究人员预计，大约90%的患MCI和存在基线病理CSF标记物的患者，将在9.2年内发展成为AD。
"因此，这些标记物能够在转变成老年痴呆症前至少5-10年鉴别出具有患AD高风险性的个体。希望那些能延缓或阻止疾病的发展新的疗法能够很快问世。结合一种早期及准确的诊断，这些疗法将能够在神经元变性还不是太普遍及患者患老年痴呆症前发挥作用，"作者总结道。（生物谷bioon.com）
doi:10.1001/archgenpsychiatry.2011.155
PMC:
PMID:
Cerebrospinal Fluid Levels of -Amyloid 1-42, but Not of Tau, Are Fully Changed Already 5 to 10 Years Before the Onset of Alzheimer Dementia
P. Buchhave, L. Minthon, H. Zetterberg, A. K. Wallin, K. Blennow, O. Hansson
Context：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. Objectives：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. Design：A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years). Setting：Memory disorder clinic. Patients：A total of 137 patients with MCI who underwent lumbar puncture at baseline. Main Outcome Measure：Conversion to AD dementia. Results：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%. Conclusions：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.
