Neuroscience Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
Aging Dis. 2023 Dec 1;14(6):1977-1980. doi: 10.14336/AD.2023.0327.
In the last few months new results in Alzheimer's (AD) and Parkinson's disease (PD) have converged, attracting attention to oligomer species of misfolded proteins, β-amyloid (Aβ and α-synuclein (α-Syn), in the pathogenesis. The high affinity for Aβ protofibrils and oligomers of lecanemab, an antibody recently approved as a disease-modifying drug in AD, and the identification of Aβ-oligomers in blood samples as early biomarkers in subjects with cognitive decline, indicate the oligomers as a therapeutic target and diagnostic tool in AD. α-Syn oligomers were identified by new histopathological techniques in the hippocampus and visual cortex of PD subjects with a distribution distinct from the Lewy body pathologies but associated with cognitive impairment; these species purified from PD brain were highly neurotoxic. In a PD experimental model, we confirmed the presence of α-Syn oligomers associated with cognitive decline and sensitive to drug treatment.
在过去的几个月里，阿尔茨海默病（AD）和帕金森病（PD）的新研究结果汇聚在一起，引起了人们对错误折叠蛋白的寡聚体物种的关注，β-淀粉样蛋白（Aβ 和 α-突触核蛋白（α-Syn）在发病机制中。一种最近被批准用于 AD 的疾病修饰药物的抗体 lecanemab 对 Aβ原纤维和寡聚体具有高亲和力，以及在认知能力下降的受试者的血液样本中发现 Aβ-寡聚体作为早期生物标志物，表明寡聚体是 AD 的治疗靶点和诊断工具。通过新的组织病理学技术在 PD 患者的海马体和视皮层中鉴定出 α-Syn 寡聚体，其分布与路易体病理不同，但与认知障碍有关；这些从 PD 大脑中纯化的物质具有高度神经毒性。在 PD 实验模型中，我们证实了与认知能力下降相关的 α-Syn 寡聚体的存在，并且对药物治疗敏感。
