Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, Mail Code 0949, La Jolla, CA, 92093, USA.
Center for Human Development, University of California, San Diego, La Jolla, CA, USA.
Acta Neuropathol Commun. 2020 Sep 10;8(1):160. doi: 10.1186/s40478-020-01033-1.
In the clinical diagnosis of dementia with Lewy bodies, distinction from Alzheimer's disease is suboptimal and complicated by shared genetic risk factors and frequent co-pathology. In the present study we tested the ability of polygenic scores for Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease to differentiate individuals in a 2713-participant, pathologically defined sample. A dementia with Lewy bodies polygenic score that excluded apolipoprotein E due to its overlap with Alzheimer's disease risk was specifically associated with at least limbic (transitional) Lewy-related pathology and a pathological diagnosis of dementia with Lewy bodies. An Alzheimer's disease polygenic score was associated with neuritic plaques and neurofibrillary tangles but not Lewy-related pathology, and was most strongly associated with an Alzheimer's pathological diagnosis. Our results indicate that an assessment of genetic risk may be useful to clinically distinguish between Alzheimer's disease and dementia with Lewy bodies. Notably, we found no association with a Parkinson's disease polygenic score, which aligns with evidence that dementia with Lewy bodies has a distinct genetic signature that can be exploited to improve clinical diagnoses.
在路易体痴呆的临床诊断中，与阿尔茨海默病的区分并不理想，并且由于存在共同的遗传风险因素和常见的共病病理，情况变得更加复杂。在本研究中，我们在一个由 2713 名参与者组成的、经病理定义的样本中测试了阿尔茨海默病、路易体痴呆和帕金森病多基因评分区分个体的能力。由于与阿尔茨海默病风险重叠，排除载脂蛋白 E 的路易体痴呆多基因评分与至少边缘（过渡）路易相关病理和路易体痴呆的病理诊断特别相关。阿尔茨海默病多基因评分与神经原纤维缠结和神经纤维缠结有关，但与路易相关病理无关，与阿尔茨海默病的病理诊断关联最强。我们的研究结果表明，遗传风险评估可能有助于临床区分阿尔茨海默病和路易体痴呆。值得注意的是，我们没有发现与帕金森病多基因评分的关联，这与以下证据一致，即路易体痴呆具有独特的遗传特征，可以用来改善临床诊断。
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