Chen X, Xia Y, Alford M, DeTeresa R, Hansen L, Klauber M R, Katzman R, Thal L, Masliah E, Saitoh T
Department of Neurosciences, University of California at San Diego, La Jolla 92093-0624, USA.
Ann Neurol. 1995 Oct;38(4):653-8. doi: 10.1002/ana.410380415.
Both genetic and environmental factors affect the progression of Alzheimer's disease (AD). The presence of cortical Lewy bodies in AD patients is associated with an altered presentation of AD pathology suggestive of an interaction between the pathogenesis of Lewy bodies and AD lesions. Since the CYP2D6B mutant allele is often present in patients with Lewy body diseases (Parkinson's disease and Lewy body variant of AD), we extended these prior observations by studying the neuropathology associated with the presence of the CYP2D6B mutant allele in a pure AD population without Lewy bodies. AD patients who possessed the CYP2D6B mutant allele, in comparison with those without the CYP2D6B allele, were found to have a smaller decline in two synaptic markers, choline acetyltransferase and synaptophysin, in the frontal cortex relative to normal control values. On the other hand, senile plaques and neurofibrillary tangles were not significantly affected by the presence of the CYP2D6B mutant allele in the frontal cortex of AD patients. Association of the CYP2D6B mutant allele with Lewy body formation in both Parkinson's disease and the Lewy body variant of AD and with the milder synaptic pathology in pure AD without Lewy bodies suggest that depending on the contribution of other genetic and environmental factors, this mutant allele may be involved with different aspects of neurodegeneration.
遗传因素和环境因素都会影响阿尔茨海默病（AD）的进展。AD患者中皮质路易小体的存在与AD病理学表现的改变有关，这提示路易小体发病机制与AD病变之间存在相互作用。由于CYP2D6B突变等位基因常出现在路易体病（帕金森病和AD的路易体变异型）患者中，我们通过研究在无路易小体的单纯AD人群中与CYP2D6B突变等位基因存在相关的神经病理学，扩展了这些先前的观察结果。与没有CYP2D6B等位基因的AD患者相比，拥有CYP2D6B突变等位基因的AD患者额叶皮质中两种突触标记物——胆碱乙酰转移酶和突触素相对于正常对照值的下降幅度较小。另一方面，AD患者额叶皮质中CYP2D6B突变等位基因的存在对老年斑和神经原纤维缠结没有显著影响。CYP2D6B突变等位基因在帕金森病和AD的路易体变异型中与路易小体形成相关，在无路易小体的单纯AD中与较轻的突触病理学相关，这表明取决于其他遗传和环境因素的作用，该突变等位基因可能参与神经退行性变的不同方面。
