Atkinson A, Singleton A B, Steward A, Ince P G, Perry R H, McKeith I G, Fairbairn A F, Edwardson J A, Daly A K, Morris C M
Medical Research Council Neurochemical Pathology Unit, Institute for the Health of the Elderly, Newcastle General Hospital, Newcastle upon Tyne, UK.
Pharmacogenetics. 1999 Feb;9(1):31-5. doi: 10.1097/00008571-199902000-00005.
The similarities between the clinical and pathological findings of dementia with Lewy Bodies (DLB) with Alzheimer's disease and Parkinson's disease are complex, and their significance for pathogenesis is unresolved. It is likely that DLB shares common disease determinants with both Alzheimer's disease and Parkinson's disease. Clinically DLB shows the presence of dementia similar, though not identical, to that found in Alzheimer's disease. A parkinsonian movement disorder is present in a proportion of DLB cases. Pathologically DLB shows senile plaques, as with Alzheimer's disease, and also substantia nigra neurone loss and Lewy bodies, as with Parkinson's disease. At a genetic level, DLB shows an elevated Apolipoprotein E epsilon4 frequency as described in Alzheimer's disease, but this is absent in Parkinson's disease. An elevated frequency of the CYP2D64 allele has been found in Parkinson's disease and we have therefore genotyped a large series of clinically and neuropathologically confirmed cases of DLB, Alzheimer's disease, Parkinson's disease and age-matched control individuals for the CYP2D64 allele. Whilst an elevated frequency of the CYP2D64 allele was found in Parkinson's disease, no such elevations were found in DLB or Alzheimer's disease. Stratification of the CYP2D64 allele with respect to the Apolipoprotein E epsilon4 also did not show any significant associations with the CYP2D64 allele. The CYP2D64 allele is not a major genetic determinant of DLB and the results place DLB with Alzheimer's disease rather than Parkinson's disease on a genetic level.
路易体痴呆（DLB）与阿尔茨海默病及帕金森病在临床和病理表现上的相似性很复杂，其对发病机制的意义尚未明确。DLB很可能与阿尔茨海默病和帕金森病有着共同的疾病决定因素。临床上，DLB表现出与阿尔茨海默病相似但不完全相同的痴呆症状。部分DLB病例存在帕金森样运动障碍。病理上，DLB与阿尔茨海默病一样有老年斑，也与帕金森病一样有黑质神经元丢失和路易小体。在基因层面，DLB如阿尔茨海默病那样表现出载脂蛋白Eε4频率升高，但帕金森病中不存在这种情况。在帕金森病中发现了CYP2D64等位基因频率升高，因此我们对大量临床和神经病理学确诊的DLB、阿尔茨海默病、帕金森病病例以及年龄匹配的对照个体进行了CYP2D64等位基因的基因分型。虽然在帕金森病中发现CYP2D64等位基因频率升高，但在DLB或阿尔茨海默病中未发现此类升高。CYP2D64等位基因与载脂蛋白Eε4的分层分析也未显示出与CYP2D64等位基因有任何显著关联。CYP2D64等位基因不是DLB的主要遗传决定因素，这些结果在基因层面上表明DLB与阿尔茨海默病更为相关，而非帕金森病。
