Gottfries C G, Lehmann W, Regland B
Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience, Göteborg University, Mölndal, Sweden.
J Neural Transm (Vienna). 1998;105(8-9):773-86. doi: 10.1007/s007020050094.
In dementia disorders, it can be assumed that the pathological process in the brain has been present for a long time. It is therefore of importance to have a preclinical or an early clinical diagnosis. Obviously, vulnerability genes, such as ApoE-4, can be diagnosed preclinically. As we have no treatment to offer patients with genetic risk factors, genotyping for ApoE-4 is at present of no clinical use. Trained neuropsychologists have today access to sensitive tests which reveal cognitive impairment before the disturbances reach the level of dementia. Laboratory investigations of cerebrospinal fluid have so far yielded no great results. Tau protein appears to be the most sensitive marker, but it is unspecific. Chromogranin A separates early onset from late onset Alzheimer's disease and seems to be a marker for synaptic degeneration. Synaptotagmin was also found to be reduced in patients with early onset Alzheimer's disease. Still we do not know, however, whether these proteins are early markers for degenerative processes in the brain. Laboratory investigations of blood have not yielded markers of use in early or differential diagnosis of dementia disorders. In a study at our own institute, however, we found serum-homocysteine (S-HCY) to be an early and sensitive marker for cognitive impairment. In patients with dysmentia (mild cognitive impairment), no less than 39% had pathological S-HCY levels, indicating insufficient 1-carbon metabolism.
在痴呆症中，可以假定大脑中的病理过程已经存在很长时间了。因此，进行临床前或早期临床诊断很重要。显然，诸如载脂蛋白E-4等易感性基因可以在临床前被诊断出来。由于我们目前没有针对具有遗传风险因素的患者的治疗方法，所以目前对载脂蛋白E-4进行基因分型没有临床用途。如今，训练有素的神经心理学家可以使用敏感的测试方法，这些方法能在认知障碍达到痴呆水平之前就检测出认知损伤。迄今为止，对脑脊液的实验室检查尚未取得显著成果。tau蛋白似乎是最敏感的标志物，但它不具有特异性。嗜铬粒蛋白A可区分早发性和晚发性阿尔茨海默病，似乎是突触退化的一个标志物。在早发性阿尔茨海默病患者中也发现突触结合蛋白减少。然而，我们仍然不知道这些蛋白质是否是大脑退化过程的早期标志物。对血液的实验室检查尚未得出可用于痴呆症早期或鉴别诊断的标志物。然而，在我们自己研究所的一项研究中，我们发现血清同型半胱氨酸（S-HCY）是认知损伤的一个早期且敏感的标志物。在患有轻度认知障碍的患者中，多达39%的患者血清同型半胱氨酸水平异常，表明一碳代谢不足。
