Department of Pathology and Experimental Therapeutics, University of Barcelona, Barcelona, Spain.
Bellvitge University Hospital, Barcelona, Spain.
Neuropathol Appl Neurobiol. 2020 Dec;46(7):654-672. doi: 10.1111/nan.12618. Epub 2020 May 1.
Most individuals with AD neuropathological changes have co-morbidities which have an impact on the integrity of the WM. This study analyses oligodendrocyte and myelin markers in the frontal WM in a series of AD cases without clinical or pathological co-morbidities.
From a consecutive autopsy series, 206 cases had neuropathological changes of AD; among them, only 33 were AD without co-morbidities. WM alterations were first evaluated in coronal sections of the frontal lobe in every case. Then, RT-qPCR and immunohistochemistry were carried out in the frontal WM of AD cases without co-morbidities to analyse the expression of selected oligodendrocyte and myelin markers.
WM demyelination was more marked in AD with co-morbidities when compared with AD cases without co-morbidities. Regarding the later, mRNA expression levels of MBP, PLP1, CNP, MAG, MAL, MOG and MOBP were preserved at stages I-II/0-A when compared with middle-aged (MA) individuals, but significantly decreased at stages III-IV/0-C. This was accompanied by reduced expression of NG2 and PDGFRA mRNA, reduced numbers of NG2-, Olig2- and HDAC2-immunoreactive cells and reduced glucose transporter immunoreactivity. Partial recovery of some of these markers occurred at stages V-VI/B-C.
The present observations demonstrate that co-morbidities have an impact on WM integrity in the elderly and in AD, and that early alterations in oligodendrocytes and transcription of genes linked to myelin proteins in WM occur in AD cases without co-morbidities. These are followed by partial recovery attempts at advanced stages. These observations suggest that oligodendrocytopathy is part of AD.
大多数具有 AD 神经病理学改变的个体都伴有合并症，这些合并症会影响 WM 的完整性。本研究分析了一系列无临床或病理合并症的 AD 病例的额 WM 中的少突胶质细胞和髓鞘标志物。
从连续尸检系列中，有 206 例病例具有 AD 的神经病理学改变；其中，只有 33 例为无合并症的 AD。在每个病例中，首先在额叶的冠状切片上评估 WM 改变。然后，对无合并症的 AD 病例的额 WM 进行 RT-qPCR 和免疫组织化学分析，以分析选定的少突胶质细胞和髓鞘标志物的表达。
与无合并症的 AD 病例相比，有合并症的 AD 患者 WM 脱髓鞘更为明显。对于后者，与中年（MA）个体相比，在 I-II/0-A 阶段 MBP、PLP1、CNP、MAG、MAL、MOG 和 MOBP 的 mRNA 表达水平得到保留，但在 III-IV/0-C 阶段显著降低。这伴随着 NG2 和 PDGFRA mRNA 表达减少、NG2-、Olig2-和 HDAC2-免疫反应性细胞数量减少和葡萄糖转运蛋白免疫反应性减少。在 V-VI/B-C 阶段，其中一些标志物出现部分恢复。
本研究观察表明，合并症对老年人和 AD 患者的 WM 完整性有影响，并且在无合并症的 AD 病例中，WM 中的少突胶质细胞和与髓鞘蛋白相关的基因转录早期发生改变。随后在晚期出现部分恢复尝试。这些观察结果表明，少突胶质细胞病变是 AD 的一部分。
