Weil Rimona S, Lashley Tammaryn L, Bras Jose, Schrag Anette E, Schott Jonathan M
Dementia Research Centre, UCL Institute of Neurology, London, UK.
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
F1000Res. 2017 Aug 30;6:1604. doi: 10.12688/f1000research.11725.1. eCollection 2017.
Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are relentlessly progressive neurodegenerative disorders that are likely to represent two ends of a disease spectrum. It is well established that both are characterised pathologically by widespread cortical Lewy body deposition. However, until recently, the pathophysiological mechanisms leading to neuronal damage were not known. It was also not understood why some cells are particularly vulnerable in PDD/DLB, nor why some individuals show more aggressive and rapid dementia than others. Recent studies using animal and cell models as well as human post-mortem analyses have provided important insights into these questions. Here, we review recent developments in the pathophysiology in PDD/DLB. Specifically, we examine the role of pathological proteins other than α-synuclein, consider particular morphological and physiological features that confer vulnerabilities on some neurons rather than others, and finally examine genetic factors that may explain some of the heterogeneity between individuals with PDD/DLB.
帕金森病痴呆（PDD）和路易体痴呆（DLB）是无情进展的神经退行性疾病，它们可能代表了疾病谱的两端。众所周知，两者在病理上均以广泛的皮质路易体沉积为特征。然而，直到最近，导致神经元损伤的病理生理机制仍不明确。人们也不明白为什么有些细胞在PDD/DLB中特别脆弱，也不明白为什么有些人比其他人表现出更具侵袭性和快速进展的痴呆。最近使用动物和细胞模型以及人体尸检分析的研究为这些问题提供了重要的见解。在这里，我们回顾PDD/DLB病理生理学的最新进展。具体而言，我们研究了除α-突触核蛋白之外的病理性蛋白质的作用，考虑了使某些神经元而非其他神经元具有易损性的特定形态和生理特征，最后研究了可能解释PDD/DLB患者个体间某些异质性的遗传因素。
