Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece.
Department of Neurology, University Hospital of Patras, School of Medicine, University of Patras, 26504 Rio Patras, Greece.
Int J Mol Sci. 2024 Feb 1;25(3):1795. doi: 10.3390/ijms25031795.
In this narrative review, we delved into the intricate interplay between alleles (typically associated with Alzheimer's disease-AD) and alpha-synucleinopathies (aS-pathies), involving Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple-system atrophy (MSA). First, in-vitro, animal, and human-based data on the exacerbating effect of on LB pathology were summarized. We found robust evidence that carriage constitutes a risk factor for PDD-APOE2, and APOE3 may not alter the risk of developing PDD. We confirmed that copies confer an increased hazard towards DLB, as well. Again and appear unrelated to the risk of conversion. Of note, in individuals with DLB , carriage appears to be intermediately prevalent between AD and PDD-PD (AD > DLB > PDD > PD). Less consistency existed when it came to PD; -PD associations tended to be markedly modified by ethnicity. Finally, we failed to establish an association between the gene and MSA. Phenotypic associations (age of disease onset, survival, cognitive-neuropsychiatric- motor-, and sleep-related manifestations) between alleles, and each of the aforementioned conditions were also outlined. Finally, a synopsis of literature gaps was provided followed by suggestions for future research.
在这篇叙述性评论中，我们深入探讨了等位基因（通常与阿尔茨海默病相关）与α-突触核蛋白病（aS-病）之间的复杂相互作用，涉及帕金森病（PD）、帕金森病痴呆（PDD）、路易体痴呆（DLB）和多系统萎缩（MSA）。首先，我们总结了关于 对 LB 病理学加剧作用的体外、动物和基于人体的数据。我们发现了强有力的证据表明 携带构成 PDD-APOE2 的风险因素，而 APOE3 可能不会改变发生 PDD 的风险。我们还证实了 拷贝数增加了 DLB 的发病风险。同样， 和 似乎与转换风险无关。值得注意的是，在患有 DLB 的个体中， 携带的比例在 AD 和 PDD-PD（AD > DLB > PDD > PD）之间似乎处于中间水平。当涉及到 PD 时，一致性较低；-PD 关联往往因种族而明显改变。最后，我们未能确定 基因与 MSA 之间存在关联。还概述了等位基因与上述每种情况之间的表型关联（疾病发病年龄、存活、认知-神经心理学-运动-和睡眠相关表现）。最后，提供了文献差距的概要，并提出了未来研究的建议。
