Psychiatric symptoms as preceding or early signs of dementia of Alzheimer type. A cohort study.

在东京都松泽医院住院的188名阿尔茨海默病(AD)患者(51名男性和137名女性)中，13.1%的女性患者和2%的男性患者出现幻觉和/或妄想作为疾病的早期症状。男性患者也有行为异常或抑郁的倾向。阿尔茨海默病患者的早期症状为抑郁、幻觉或妄想，常被神经病理学诊断为路易体痴呆(DLB)。绝大多数DLB患者与AD患者一样，边缘皮质中淀粉样β蛋白(Aβ)大量积聚和神经纤维性改变。另一方面，那些不符合DLB标准并因此被诊断为AD的人，通常有轻微的路易体病变。提示阿尔茨海默病患者精神症状的发生可能与AD灶与DLB灶的重叠有关。然而，将这两种疾病放在一个单独的实体或一组疾病中考虑，一个尚未解决的问题是DLB新皮质中缺乏神经纤维变化，这似乎与Aβ沉积的程度不成比例。在这项研究中，我们用磷酸化的α-突触核蛋白抗体对死后弥漫性脑白质损伤患者的死后脑组织进行免疫组织化学染色，证明α-突触核蛋白在弥漫性脑白质瘤新皮质的神经元突起中大量积聚。定量分析表明，阿尔茨海默病中神经源性α-突触核蛋白的积累量与AD时神经源性tau的积累量相当。神经元性α-突触核蛋白和tau的总积聚与Aβ沉积的程度成正比，无论是DLB型还是AD型。β不仅可以促进tau的积累，还可以促进α-突触核蛋白的积累。我们推测，如果过程转向tau积聚，则表现为AD，如果转向α-突触核蛋白积聚，则表现为DLb

In total of 188 Alzheimer's disease (AD) patients (51 men and 137 women), who were admitted to Tokyo Metropolitan Matsuzawa Hospital, 13.1% of female patients and 2% of male patients had hallucination and/or delusion as early symptoms of the disease. The male patients also tended to have abnormal behavior or depression. Patients with AD type dementia, who show depression, hallucination or delusion as early symptoms, are often diagnosed neuropathologically as dementia with Lewy bodies (DLB). The vast majority of DLB patients had heavy accumulation of amyloid beta protein (Aβ) and neurofibrillary changes in the limbic cortices similarly to AD patients. On the other hand, those who do not fulfill the criteria for DLB and are, thus, diagnosed as AD, often have mild Lewy body pathology. It seems that the occurrence of psychiatric symptoms in dementia of AD type is related to the overlap between AD lesions and DLB lesions. However, thinking of these two diseases in a single entity or a group of diseases, a yet unsolved question is paucity of neurofibrillary changes in the neocortex of DLB, which seems to be unproportionate to the degree of Aβ deposits. In this study, we have demonstrated heavy accumulation of α-synuclein in the neuronal processes in the neocortex of DLB by immunohistochemistry of postmortem brain tissues from DLB patients using the antibodies to phosphorylated α-synuclein. Quantitative analyses have indicated that the amount of neuritic α-synuclein accumulation in DLB is comparable with that of neuritic tau accumulation in AD. The total of neuritic α-synuclein and tau accumulation is proportionate to the degree of Aβ deposits regardless of the cases is DLB or AD. Aβ may promote accumulation of not only tau but also α-synuclein. We speculate that, if the process is shifted toward tau accumulation, the manifestation becomes AD, and, if it is shifted toward α-synuclein accumulation, the manifestation becomes DLB