Badihian Negin, Tosakulwong Nirubol, Weigand Stephen D, Ali Farwa, Clark Heather M, Stierwalt Julie, Botha Hugo, Savica Rodolfo, Dickson Dennis W, Whitwell Jennifer L, Josephs Keith A
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Parkinsonism Relat Disord. 2024 Oct;127:107109. doi: 10.1016/j.parkreldis.2024.107109. Epub 2024 Aug 17.
A definitive diagnosis of progressive supranuclear palsy (PSP) can only be established through neuropathological evaluations where four cardinal tau lesions are identified. Relationships between regional tau burden and disease duration/age at death is unclear.
To investigate relationships between tau burden in different brain regions and disease duration and age at death in PSP and determine whether association are influenced by PSP subtype (subcortical/cortical) or co-pathologies.
We identified 45 patients with definite PSP who were evaluated at Mayo Clinic between 2009 and 2023, died and underwent histopathological evaluation. We performed semi-quantitative lesion count for each of four cardinal lesions (pretangles/globose neurofibrillary tangles, threads, tufted astrocytes, and coiled bodies) across 10 brain regions. We fit Bayesian linear hierarchical regression models to estimate the relationship between total pathological burden, and disease duration and age at death by region and the influence of subtype and co-pathologies.
Of the 45 patients, 18 (40 %) were female. Median age at death was 75 (56-87) years and median disease duration was 8 (3,15) years. Younger age at death was associated with greater total tau burden in the pallidum, red nucleus, striatum, and subthalamic nucleus (all p ≤ 0.01). Shorter disease duration was associated with greater total tau burden in the red nucleus (p = 0.05). There was no evidence for a difference in association between lesion types. PSP subtype and co-pathologies did not influence associations.
The findings from this study suggest that age and disease duration influence burden of tau pathology in subcortical regions in PSP.
进行性核上性麻痹（PSP）的明确诊断只能通过神经病理学评估来确定，其中要识别出四种主要的tau病变。区域tau负担与疾病持续时间/死亡年龄之间的关系尚不清楚。
研究PSP患者不同脑区的tau负担与疾病持续时间和死亡年龄之间的关系，并确定这些关联是否受PSP亚型（皮质下/皮质）或合并病理情况的影响。
我们确定了45例2009年至2023年期间在梅奥诊所接受评估、死亡并接受组织病理学评估的明确PSP患者。我们对10个脑区的四种主要病变（前缠结/球状神经原纤维缠结、细丝、簇状星形胶质细胞和螺旋体）中的每一种进行了半定量病变计数。我们拟合了贝叶斯线性分层回归模型，以估计总病理负担与按区域划分的疾病持续时间和死亡年龄之间的关系，以及亚型和合并病理情况的影响。
45例患者中，18例（40%）为女性。死亡时的中位年龄为75（56 - 87）岁，中位疾病持续时间为8（3，15）年。死亡时年龄较小与苍白球、红核、纹状体和丘脑底核中更高的总tau负担相关（所有p≤0.01）。疾病持续时间较短与红核中更高的总tau负担相关（p = 0.05）。没有证据表明病变类型之间的关联存在差异。PSP亚型和合并病理情况不影响关联。
本研究结果表明，年龄和疾病持续时间会影响PSP患者皮质下区域的tau病理负担。
