Abstract:
Concomitant Alzheimer\'s disease (AD) pathology is a frequent event in the context of Lewy body disease (LBD), occurring in approximately half of all cases. Evidence shows that LBD patients with AD copathology show an accelerated disease course, a greater risk of cognitive decline and an overall poorer prognosis. However, LBD-AD cases may show heterogeneous motor and non-motor phenotypes with higher risk of dementia, and, consequently, be not rarely misdiagnosed. In this review, we summarize the state-of-the-art on LBD-AD by discussing the synergistic effects between AD neuropathological changes and Lewy pathology and their clinical relevance. Furthermore, we provide an extensive overview of neuroimaging and fluid biomarkers under assessment in LBD-AD and their possible diagnostic and prognostic value. AD pathology can be suspected in vivo by means of CSF, MRI and PET markers, whereas α-synuclein seed amplification assays (SAAs) represent to date the most promising technique to identify Lewy pathology in different biological tissues. Pathological imaging and CSF AD biomarkers are associated with a higher likelihood of cognitive decline in LBD but do not always mirror the neuropathological severity like in pure AD. The implementation of blood-based biomarkers of AD might allow the fast screening of LBD patients for AD copathology, thus improving the overall diagnostic sensitivity for LBD-AD. Finally, we discuss the literature on novel candidate biomarkers being exploited in LBD-AD to investigate other aspects of neurodegeneration, such as neuroaxonal injury, glial activation and synaptic dysfunction. The thorough characterization of AD copathology in LBD should be taken into account for the differential diagnosis of dementia syndromes, for the prognostic evaluation on an individual level and for guiding symptomatic and disease-modifying therapies.
摘要:
伴随阿尔茨海默病(AD)病理是路易体病(LBD)的常见事件,发生在大约一半的病例中。证据表明,患有AD的LBD患者表现出加速的病程,认知功能下降的风险更大,总体预后较差。然而,LBD-AD病例可能表现出异质性运动和非运动表型,痴呆风险较高,and,因此,很少被误诊。在这次审查中,我们通过讨论AD神经病理学改变与Lewy病理学之间的协同作用及其临床相关性来总结LBD-AD的最新研究进展。此外,我们对LBD-AD的神经影像学和体液生物标志物及其可能的诊断和预后价值进行了广泛的概述.AD病理可以通过CSF在体内怀疑,MRI和PET标记,而α-突触核蛋白种子扩增测定(SAAs)代表了迄今为止在不同生物组织中鉴定路易病理的最有前途的技术。病理成像和CSFAD生物标志物与LBD中认知下降的较高可能性相关,但并不总是像纯AD那样反映神经病理严重程度。基于血液的AD生物标志物的实施可能允许快速筛查LBD患者的AD共病理学。从而提高LBD-AD的整体诊断灵敏度。最后,我们讨论了在LBD-AD中利用新的候选生物标志物来研究神经变性的其他方面的文献,比如神经轴索损伤,神经胶质激活和突触功能障碍。在鉴别诊断痴呆综合征时,应考虑LBD中AD共病理学的全面表征。用于个体水平的预后评估以及指导对症和疾病改善疗法。