Abstract

There is mounting evidence that Parkinson’s disease (PD) and Alzheimer’s disease (AD) share neuropathological hallmarks, while similar types of biomarkers are being applied to both. In this review we aimed to explore similarities and differences between PD and AD at both the neuropathology and the biomarker levels, specifically focusing on protein aggregates and synapse dysfunction. Thus, amyloid-β peptide (Aβ) and tau lesions of the Alzheimer-type are common in PD and α-synuclein Lewy-type aggregates are frequent findings in AD. Modern neuropathological techniques adding to routine immunohistochemistry might take further our knowledge of these diseases beyond protein aggregates and down to their presynaptic and postsynaptic terminals, with potential mechanistic and even future therapeutic implications. Translation of neuropathological discoveries to the clinic remains challenging. Cerebrospinal fluid (CSF) and positron emission tomography (PET) markers of Aβ and tau have been shown to be reliable for AD diagnosis. Conversely, CSF markers of α-synuclein have not been that consistent. In terms of PET markers, there is no PET probe available for α-synuclein yet, while the AD PET markers range from consistent evidence of their specificity (amyloid imaging) to greater uncertainty of their reliability due to off-target binding (tau imaging). CSF synaptic markers are attractive, still needing more evidence, which currently suggests those might be non-specific markers of disease progression. It can be summarized that there is neuropathological evidence that protein aggregates of AD and PD are present both at the soma and the synapse. Thus, a number of CSF and PET biomarkers beyond α-synuclein, tau and Aβ might capture these different faces of protein-related neurodegeneration. It remains to be seen what the longitudinal outcomes and the potential value as surrogate markers of these biomarkers are.

中文翻译：

---

帕金森病和阿尔茨海默病的神经病理学和生物标志物发现：从蛋白质聚集体到突触功能障碍

摘要

越来越多的证据表明，帕金森病 (PD) 和阿尔茨海默病 (AD) 具有共同的神经病理学特征，而相似类型的生物标志物正被应用于两者。在这篇综述中，我们旨在探讨 PD 和 AD 在神经病理学和生物标志物水平上的异同，特别关注蛋白质聚集和突触功能障碍。因此，淀粉样蛋白 β 肽 (Aβ) 和阿尔茨海默型 tau 病变在 PD 中很常见，而 α-突触核蛋白路易型聚集体在 AD 中很常见。添加到常规免疫组织化学的现代神经病理学技术可能会使我们对这些疾病的了解进一步超出蛋白质聚集体，并深入到它们的突触前和突触后末端，具有潜在的机制甚至未来的治疗意义。将神经病理学发现转化为临床仍然具有挑战性。Aβ 和 tau 的脑脊液 (CSF) 和正电子发射断层扫描 (PET) 标志物已被证明可用于 AD 诊断。相反，α-突触核蛋白的脑脊液标志物并不一致。就 PET 标记而言，目前还没有可用于 α-突触核蛋白的 PET 探针，而 AD PET 标记的范围从其特异性的一致证据（淀粉样蛋白成像）到由于脱靶结合而导致的可靠性的更大不确定性（tau 成像） . CSF 突触标志物很有吸引力，但仍需要更多证据，目前这表明这些标志物可能是疾病进展的非特异性标志物。可以总结出，有神经病理学证据表明 AD 和 PD 的蛋白质聚集体同时存在于体细胞和突触中。因此，除了 α-突触核蛋白、tau 和 Aβ 之外，许多 CSF 和 PET 生物标志物可能会捕捉蛋白质相关神经变性的这些不同方面。纵向结果和作为这些生物标志物替代标志物的潜在价值还有待观察。