Kumar Mahesh, Roemer Shanu F, Tosakulwong Nirubol, Weigand Stephen D, Ali Farwa, Clark Heather M, Stierwalt Julie, Savica Rodolfo, Dickson Dennis W, Whitwell Jennifer L, Josephs Keith A
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Parkinsonism Relat Disord. 2025 Jul 30;139:107980. doi: 10.1016/j.parkreldis.2025.107980.
Neuronal loss and the presence of tau lesions in specific brain regions is required for a definitive diagnosis of progressive supranuclear palsy (PSP). We previously found tau burden in basal ganglia and red nucleus to be associated with disease duration and age at death. It is currently unknown whether neuronal loss is also associated with disease duration and age at death, or with antemortem brain volume loss in PSP.
To investigate whether neuronal loss is associated with tau burden, age at death, disease duration, or brain volume loss in PSP.
Forty-one pathologically confirmed PSP participants prospectively recruited and followed by the Neurodegenerative Research Group (NRG), Mayo Clinic, MN, between 2009 and 2023, of which 40 completed antemortem MRI, were analyzed. Neuronal loss in the subthalamic and red nuclei was determined on hematoxylin and eosin. Multinomial logistic regressions with age at death, disease duration, and brain volume as independent variables, and regional neuronal loss as outcome, were performed.
Fourteen participants (34 %) were female, median age at death was 74 years [68, 79], and median disease duration was 8.2 years [5.7, 9.9]. Greater neuronal loss was associated with greater burden of glial, but not neuronal, tau lesions in both nuclei. Greater neuronal loss was associated with shorter disease duration in both nuclei, particularly in the subthalamic nucleus, and smaller volume on MRI of the red nucleus.
Neuronal loss in subthalamic and red nuclei, cardinal PSP regions, appear to be playing a role in disease duration and brain volume loss in PSP.
特定脑区出现神经元丢失和tau病变是进行性核上性麻痹（PSP）明确诊断的必要条件。我们之前发现基底神经节和红核中的tau负荷与疾病持续时间和死亡年龄相关。目前尚不清楚神经元丢失是否也与PSP的疾病持续时间、死亡年龄或生前脑容量损失有关。
研究PSP中神经元丢失是否与tau负荷、死亡年龄、疾病持续时间或脑容量损失有关。
分析了2009年至2023年间由梅奥诊所神经退行性疾病研究组（NRG）前瞻性招募并随访的41名经病理证实的PSP参与者，其中40人完成了生前MRI检查。苏木精和伊红染色确定丘脑底核和红核中的神经元丢失情况。以死亡年龄、疾病持续时间和脑容量为自变量，区域神经元丢失为结果进行多项逻辑回归分析。
14名参与者（34%）为女性，中位死亡年龄为74岁[68, 79]，中位疾病持续时间为8.2年[5.7, 9.9]。两个核中神经元丢失增加与胶质细胞而非神经元tau病变的负荷增加相关。两个核中神经元丢失增加与疾病持续时间缩短相关，尤其是在丘脑底核，且红核MRI体积较小。
丘脑底核和红核（PSP的主要区域）中的神经元丢失似乎在PSP的疾病持续时间和脑容量损失中起作用。
