Sodeyama N, Itoh Y, Suematsu N, Matsushita M, Otomo E, Mizusawa H, Yamada M
Department of Neurology, Tokyo Medical and Dental University, Japan.
J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):548-51. doi: 10.1136/jnnp.64.4.548.
A genetic association between the presenilin 1 (PS-1) intronic polymorphism and sporadic Alzheimer's disease has been a matter of controversy. Recent findings have suggested that the PS-1 polymorphism is not associated with Alzheimer's disease or amyloid beta-protein (Abeta) deposition in brains from patients with Alzheimer's disease.
To elucidate the influence of the PS-1 polymorphism on Alzheimer type neuropathological changes and the development of Alzheimer's disease, the relation between the PS-1 polymorphism and quantitative severity of Alzheimer type neuropathological changes in the brains from patients with Alzheimer's disease and non-demented subjects was studied.
The PS-1 and apolipoprotein E (ApoE) genotypes, were examined, together with the densities of the senile plaques, senile plaques with dystrophic neurites, and neurofibrillary tangles in the brains from 36 postmortem confirmed patients with sporadic Alzheimer's disease and 86 non-demented subjects. Association of the PS-1 polymorphism with sporadic Alzheimer's disease and ages at onset and duration of illness in Alzheimer's disease was also examined.
The PS-1 polymorphism was not associated with the senile plaques, senile plaques with dystrophic neurites, or neurofibrillary tangles in Alzheimer's disease or non-demented subjects. There was no association of the PS-1 intronic polymorphism with Alzheimer's disease, ages at onset, or durations of illness in Alzheimer's disease. The results remained nonsignificant even when the PS-1 genotype groups were divided into the subgroups with different ApoE epsilon4 status.
The PS-1 intronic polymorphism does not itself have a direct causal role in the formation of Alzheimer type neuropathological changes or in the development of sporadic Alzheimer's disease.
早老素1（PS - 1）内含子多态性与散发性阿尔茨海默病之间的基因关联一直存在争议。最近的研究结果表明，PS - 1多态性与阿尔茨海默病患者大脑中的阿尔茨海默病或β淀粉样蛋白（Aβ）沉积无关。
为阐明PS - 1多态性对阿尔茨海默型神经病理变化及阿尔茨海默病发展的影响，研究了PS - 1多态性与阿尔茨海默病患者及非痴呆受试者大脑中阿尔茨海默型神经病理变化的定量严重程度之间的关系。
检测了36例经尸检确诊的散发性阿尔茨海默病患者及86例非痴呆受试者大脑中的PS - 1和载脂蛋白E（ApoE）基因型，以及老年斑、伴有营养不良性神经突的老年斑和神经原纤维缠结的密度。还研究了PS - 1多态性与散发性阿尔茨海默病、发病年龄及阿尔茨海默病病程的关联。
PS - 1多态性与阿尔茨海默病患者及非痴呆受试者的老年斑、伴有营养不良性神经突的老年斑或神经原纤维缠结无关。PS - 1内含子多态性与阿尔茨海默病、发病年龄或阿尔茨海默病病程均无关联。即使将PS - 1基因型组按不同的ApoE ε4状态分为亚组，结果仍无统计学意义。
PS - 1内含子多态性本身在阿尔茨海默型神经病理变化的形成或散发性阿尔茨海默病的发展中没有直接因果作用。
