Institute of Clinical Neurobiology, Alberichgasse 5/13, A-1150, Vienna, Austria.
Parkinsonism Relat Disord. 2023 Feb;107:105273. doi: 10.1016/j.parkreldis.2022.105273. Epub 2022 Dec 30.
To compare the neuropathology between two types of multiple system atrophy - parkinsonism-predominant (MSA-P) and cerebellar ataxia-predominant (MSA-C) with cognitive impairment.
MATERIAL & METHODS: 35 cases of MSA-P (mean age at death 60.5 ± 7.8 years) and 15 cases of MSA-C (mean age at death 61.3 ± 6.8 years), 35.% of which associated with mild to moderate cognitive impairment and one with severe dementia, were examined neuropathologically with semiquantitative evaluation of both α-synuclein and Alzheimer pathologies, including cerebral amyloid angiopathy (CAA) and other co-pathologies.
While the mean age at death of both MSA subgroups was similar, the age at onset and duration of disease were slightly higher in the MSA-C group. In line with the classification, the αSyn pathology glial and neuronal inclusions in both the cortex and brainstem were significantly higher in the MSA-P group. With regard to the Alzheimer disease pathology, tau load in cases with mild to moderate cognitive impairment was slightly but not significantly higher in the MSA-P group, one with severe dementia showing fully developed Alzheimer co-pathology, while the amyloid-β (Aβ) load including the CAA was higher in the MSA-C group. The presence of Lewy co-pathology in this series (20%), being similar to that of other MSA cohorts, was more frequent in MSA cases with mild to severe cognitive impairment, but did not differ between the two subgroups and seems not essentially important for MCI in MSA.
In agreement with previous clinical studies that reported more severe cognitive dysfunction in patients with MSA-P, the present neuropathological study showed increased tau pathology in MSA-P and one with severe Alzheimer co-pathology, but only slightly increased amyloid pathology in the MSA-C group. Lewy co-pathology was more frequent in MSA-P cases with cognitive decline. In view of the limited data about the pathobiological basis of cognitive impairment in MSA, further studies to elucidate the differences between the two phenotypes are urgently needed.
比较两种多系统萎缩 - 帕金森病为主型（MSA-P）和小脑共济失调为主型（MSA-C）伴认知障碍的神经病理学。
35 例 MSA-P（死亡时平均年龄 60.5±7.8 岁）和 15 例 MSA-C（死亡时平均年龄 61.3±6.8 岁），其中 35%伴有轻度至中度认知障碍，1 例伴有严重痴呆，进行了神经病理学检查，包括 α-突触核蛋白和阿尔茨海默病病理学（包括脑淀粉样血管病 [CAA] 和其他共病）的半定量评估。
尽管两个 MSA 亚组的死亡时平均年龄相似，但 MSA-C 组的发病年龄和疾病持续时间略高。与分类一致，MSA-P 组皮质和脑干的 αSyn 病理学神经胶质和神经元包涵体明显更高。关于阿尔茨海默病病理学，轻度至中度认知障碍病例的 tau 负荷在 MSA-P 组略高但无统计学意义，1 例伴有严重痴呆的病例表现出完全发育的阿尔茨海默共病，而淀粉样-β（Aβ）负荷包括 CAA 在 MSA-C 组更高。本系列（20%）Lewy 共病的存在与其他 MSA 队列相似，在轻度至重度认知障碍的 MSA 病例中更为常见，但在两个亚组之间无差异，似乎对 MSA 的 MCI 不重要。
与先前报道 MSA-P 患者认知功能障碍更严重的临床研究一致，本神经病理学研究显示 MSA-P 中 tau 病理学增加，1 例伴有严重的阿尔茨海默共病，但 MSA-C 组的淀粉样蛋白病理学仅略有增加。Lewy 共病在伴有认知下降的 MSA-P 病例中更为常见。鉴于关于 MSA 认知障碍的病理生物学基础的有限数据，迫切需要进一步研究以阐明两种表型之间的差异。
