Andreasen N, Vanmechelen E, Van de Voorde A, Davidsson P, Hesse C, Tarvonen S, Räihä I, Sourander L, Winblad B, Blennow K
Department of Rehabilitation, Piteå River Valley Hospital, Sweden.
J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):298-305. doi: 10.1136/jnnp.64.3.298.
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 Piteå 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.
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.
Concentrations of total (both normal tau and PHF-tau) tau in CSF, clinical measures (duration and severity of dementia), and apoE polymorphism.
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.
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.
阿尔茨海默病的生化标志物具有重要价值，尤其有助于在疾病进程早期进行诊断。大多数阿尔茨海默病患者脑脊液tau蛋白（CSF-tau）显著升高。然而，其特异性仍需进一步研究，因为在其他痴呆症中也发现了CSF-tau升高，特别是在血管性痴呆中。由于之前大多数脑脊液研究基于选定的住院患者，因此考察CSF-tau在以社区人群为基础的连续性痴呆患者样本中的诊断潜力具有特殊意义。自1986年以来，瑞典北部皮特奥河谷医院对这类患者样本进行了检查，包括社区中所有有记忆障碍的患者。目的还在于研究CSF-tau升高是否在疾病进程早期出现，以及CSF-tau在疾病进展过程中是否发生变化。
以社区人群为基础的样本，包括75例痴呆患者（43例阿尔茨海默病患者、21例血管性痴呆患者和11例阿尔茨海默病/血管性痴呆混合型患者）、18名健康受试者和18名神经科对照者。约一年后对所有患者进行了随访调查（包括分析新的脑脊液样本）。
脑脊液中总tau蛋白（正常tau蛋白和PHF-tau蛋白）的浓度、临床指标（痴呆的病程和严重程度）以及载脂蛋白E基因多态性。
阿尔茨海默病患者CSF-tau显著升高，41/43（95%）的患者值高于对照组的临界水平（均值+2标准差）（306 pg/ml）。大多数血管性痴呆患者也发现了高CSF-tau浓度，优先出现在CT上无进行性脑白质疏松的血管性痴呆患者中，而有进行性脑白质疏松的血管性痴呆患者CSF-tau正常。阿尔茨海默病患者和血管性痴呆患者在一年随访时CSF-tau浓度稳定，且CSF-tau与痴呆的病程或严重程度均无相关性。
研究结果证实了CSF-tau对阿尔茨海默病诊断的高敏感性，但在血管性痴呆中也发现了高CSF-tau，导致特异性较低。然而，高CSF-tau优先出现在无进行性脑白质疏松的血管性痴呆患者中，这可能构成一组伴有阿尔茨海默病病理改变的人群。在阿尔茨海默病中，高CSF-tau可能在疾病全过程中都存在。因此，在临床痴呆发作之前可能就已存在相同的高CSF-tau浓度。对此类患者的随访研究将揭示CSF-tau分析作为早期阿尔茨海默病生化标志物是否有用。
