Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease:: a community based follow up study
Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease:: a community based follow up study
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DOI：
10.1136/jnnp.64.3.298
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发表时间：
1998-03-01
影响因子：
11
通讯作者：
Blennow, K
中科院分区：
文献类型：
--
作者：
Andreasen, N;Vanmechelen, E;Blennow, K
目的：阿尔茨海默病的生化标志物具有重要的价值，特别是有助于疾病早期诊断。在大多数阿尔茨海默病患者中发现CSF tau蛋白（CSF-tau）显著增加。然而，特异性还有待进一步研究，因为在其他痴呆症中也发现了CSF-tau的增加，特别是在血管性痴呆症中。由于大多数先前的CSF研究都是基于选定的住院患者，因此认为特别感兴趣的是在基于社区人群的连续痴呆患者样本中检查CSF-tau的诊断潜力。自1986年以来，瑞典北方的皮蒂亚河谷医院一直在检查这些病人的资料，其中包括社区中所有记忆障碍的人。的目的也是研究，如果发现在CSF-tau蛋白的增加在疾病过程中的早期，以及是否CSF-tau蛋白的变化在疾病的进展过程中。方法-参与者：社区人口为基础的样本75痴呆患者（43阿尔茨海默氏病，21血管性痴呆，11与混合阿尔茨海默氏病/血管性痴呆），18名健康受试者，和18个神经控制。后续调查在大约一年后在所有患者中进行（包括新的CSF样品的分析）。（正常tau和PHF-tau）CSF中的tau，临床测量结果-CSF-tau蛋白在阿尔茨海默病患者中显著升高，41/43例（95%）患者的数值高于对照组的临界水平（平均值± 2 SD）（306 pg/ml）。在大多数血管性痴呆患者中也发现了高CSF-tau浓度，优选在CT上没有进行性脑白质疏松的血管性痴呆患者中，而具有进行性脑白质疏松的血管性痴呆患者具有正常CSF-tau。CSF-tau的浓度是稳定的，在一年的随访在阿尔茨海默病患者和血管性痴呆患者，并有CSF-tau和无论是持续时间或严重程度dementions. Conclusions的研究结果之间没有相关性证实CSF-tau诊断阿尔茨海默病的高敏感性，但高CSF-tau也被发现在血管性痴呆，导致在较低的特异性。然而，高CSF-tau蛋白优先见于无进行性脑白质疏松的血管性痴呆患者，这可能构成伴随阿尔茨海默病病理的一组。高CSF-tau可能存在于阿尔茨海默病的整个病程中。因此，在临床痴呆发作之前可能存在相同的高CSF-tau浓度。对此类患者的后续研究将表明CSF-tau分析是否可用作早期阿尔茨海默病的生化标志物。
Objectives-Biochemical markers for Alzheimer's disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer's disease. However, the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia. As most previous CSF studies have been based on selected inpatients, it was considered of special interest to examine the diagnostic potential of CSF-tau in a community population based sample of consecutive patients with dementia. Such patient material has been examined at the Pitea River Valley Hospital in Northern Sweden since 1986, and includes all those with memory disturbances in the community. The aim was also to study if an increase in CSF-tau is found early in the disease process, and whether CSF-tau changes during the progression of disease.Methods-Participants: Community population based sample of 75 demented patients (43 with Alzheimer's disease, 21 with vascular dementia, and 11 with mixed Alzheimer's disease/vascular dementia), 18 healthy subjects, and 18 neurological controls. A follow up investigation (including analysis of a new CSF sample) was performed in all patients after about one year.Main outcome measures-Concentrations of total (both normal tau and PHF-tau) tau in CSF, clinical measures (duration and severity of dementia), and apoE polymorphism.Results-CSF-tau was markedly increased in Alzheimer's disease, 41/43 (95%) patients had values above the cut off level (mean+2 SD) in controls (306 pg/ml). High CSF-tau concentrations were also found in most patients with vascular dementia, preferentially in patients with vascular dementia without progressive leukoaraiosis on CT, whereas patients with vascular dementia with progressive leukoaraiosis had normal CSF-tau. Concentrations of CSF-tau were stable at one year follow up in both patients with Alzheimer's disease and patients with vascular dementia, and there was no correlation between CSF-tau and either duration or severity of dementia.Conclusions-The findings confirm the high sensitivity of CSF-tau for the diagnosis of Alzheimer's disease, but high CSF-tau was also found in vascular dementia, resulting in a lower specificity. However, high CSF-tau is preferentially found in patients with vascular dementia without progressive leukoaraiosis, which may constitute a group with concomitant Alzheimer's disease pathology. High CSF-tau may be present during the whole course of the disease in Alzheimer's disease. Possibly, therefore, the same high CSF-tau concentrations may be present before the onset of clinical dementia. Follow up studies on such patients will tell whether analysis of CSF-tau is useful as a biochemical marker for early Alzheimer's disease.