Lavados Manuel, Farías Gustavo, Rothhammer Francisco, Guillon Marta, Mujica Maria C, Maccioni Cristóbal, Maccioni Ricardo B
Department of Neurological Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Arch Med Res. 2005 Sep-Oct;36(5):474-9. doi: 10.1016/j.arcmed.2005.03.036.
The presence of brain hyperphosphorylated tau constitutes a hallmark of neurodegenerative disorders of the Alzheimer's type. This report describes the relationships between tau markers in the cerebrospinal fluid (CSF), the degree of cognitive impairment and the predictive value of genetic markers such the alleles of apolipoprotein E, namely, the presence of Apo-epsilon4, as part of a longitudinal study.
Three major groups of patients with ages ranging from 65-73 years were evaluated in this study (n=72): Alzheimer's disease patients (AD), a group with mild cognitive impairment (MCI) and normal senile patients (NS). Hyperphosphorylated tau and tau dephosphorylated species at the Alzheimer-type epitopes in CSF samples were analyzed by ELISA assays using a battery of different monoclonal antibodies. ApoE was analyzed by PCR in blood samples.
The levels of hyperphosphorylated tau were significantly higher in AD patients, but no statistical differences were found between the MCI and NS groups. However, the analysis of tau markers and cognitive impairment indicated the existence of two main subgroups within this population: MCI patients with a higher cognitive impairment as revealed by the total box score (TBS) >1.5 who exhibited phosphorylated tau patterns similar to the AD group, and patients with a mild impairment (TBS <1.5) with tau patterns similar to normal patients. In regard to ApoE, epsilon4/epsilon4 genotype was absent in the Chilean population analyzed, and only the epsilon2/epsilon4 genotype was significantly increased in both MCI and AD patients. A detailed analysis of the ApoE alleles, particularly epsilon3 and epsilon4, indicated a tendency to increase the epsilon4 allele in the MCI group with higher cognitive impairment and in AD patients.
Studies indicate that hyperphosphorylated tau is a good indicator of the degree of cognitive disorders in early stages of AD and that no clear correlation exists with the epsilon4/epsilon4 and epsilon3/epsilon4 genotypes, even though a higher proportion of epsilon4 allele in the MCI group with a more significant level of impairment and in AD patients was evidenced.
脑内过度磷酸化tau蛋白的存在是阿尔茨海默病型神经退行性疾病的一个标志。本报告作为一项纵向研究的一部分，描述了脑脊液（CSF）中tau蛋白标志物、认知障碍程度以及载脂蛋白E等位基因等遗传标志物（即Apo-ε4的存在）之间的关系。
本研究评估了三组年龄在65 - 73岁之间的主要患者群体（n = 72）：阿尔茨海默病患者（AD）、轻度认知障碍组（MCI）和正常老年患者（NS）。使用一系列不同的单克隆抗体，通过ELISA检测分析CSF样本中阿尔茨海默病型表位处的过度磷酸化tau蛋白和去磷酸化tau蛋白种类。通过PCR分析血样中的ApoE。
AD患者中过度磷酸化tau蛋白水平显著更高，但MCI组和NS组之间未发现统计学差异。然而，对tau蛋白标志物和认知障碍的分析表明该人群中存在两个主要亚组：总方框评分（TBS）>1.5显示认知障碍较高的MCI患者，其磷酸化tau蛋白模式与AD组相似；以及轻度障碍（TBS <1.5）且tau蛋白模式与正常患者相似的患者。关于ApoE，在所分析的智利人群中不存在ε4/ε4基因型，并且仅ε2/ε4基因型在MCI和AD患者中均显著增加。对ApoE等位基因，特别是ε3和ε4的详细分析表明，在认知障碍较高的MCI组和AD患者中，ε4等位基因有增加的趋势。
研究表明，过度磷酸化tau蛋白是AD早期认知障碍程度的良好指标，并且与ε4/ε4和ε3/ε4基因型不存在明确相关性，尽管在损伤程度更显著的MCI组和AD患者中，ε4等位基因的比例更高得到了证实。
