National Institute on Aging, Layton Aging & Alzheimer's Disease Research Center, Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
Department of Neurology, Portland Veterans Affairs Health Care System, Portland, Oregon, USA.
Alzheimers Dement. 2024 Jun;20(6):3839-3851. doi: 10.1002/alz.13816. Epub 2024 Apr 17.
Age-related magnetic resonance imaging (MRI) T2 white matter hyperintensities (WMHs) are common and associated with neurological decline. We investigated the histopathological underpinnings of MRI WMH and surrounding normal appearing white matter (NAWM), with a focus on astroglial phenotypes.
Brain samples from 51 oldest old Oregon Alzheimer's Disease Research Center participants who came to autopsy underwent post mortem (PM) 7 tesla MRI with targeted histopathological sampling of WMHs and NAWM. Stained slides were digitized and quantified. Mixed-effects models determined differences in molecular characteristics between WMHs and the NAWM and across NAWM.
PM MRI-targeted WMHs are characterized by demyelination, microglial activation, and prominent astrocytic alterations, including disrupted aquaporin (AQP) expression. Similar changes occur within the surrounding NAWM in a pattern of decreasing severity with increased distance from WMHs.
Decreased AQP expression within WMH and proximal NAWM suggest an overwhelmed system wherein water homeostasis is no longer maintained, contributing to WM damage in older individuals.
Post mortem magnetic resonance imaging (MRI) was used to characterize the pathology of white matter hyperintensities (WMHs) and surrounding normal appearing white matter (NAWM). Stained immunohistochemical (IHC) slides from targeted WMH and NAWM samples were digitized and quantified. WMHs and NAWM were associated with inflammation, demyelination, and gliosis. WMHs and NAWM astrocytic changes included decreased AQP1 and AQP4 expression. Abnormal NAWM pathology diminished in severity with increasing distance from WMH.
与年龄相关的磁共振成像（MRI）T2 脑白质高信号（WMHs）很常见，并且与神经功能下降有关。我们研究了 MRI WMH 及其周围正常表现的白质（NAWM）的组织病理学基础，重点研究星形胶质细胞表型。
来自俄勒冈州阿尔茨海默病研究中心的 51 名年龄最大的参与者在死后（PM）接受了 7 特斯拉 MRI 检查，对 WMH 和 NAWM 进行了靶向组织病理学采样。对染色载玻片进行数字化和量化。混合效应模型确定了 WMH 和 NAWM 之间以及 NAWM 内部的分子特征差异。
PM MRI 靶向的 WMH 表现为脱髓鞘、小胶质细胞激活和明显的星形胶质细胞改变，包括水通道蛋白（AQP）表达中断。在 WMH 周围的 NAWM 中也发生了类似的变化，其模式为随着与 WMH 距离的增加而逐渐减轻。
WMH 和邻近 NAWM 内 AQP 表达减少表明系统不堪重负，水动态平衡不再维持，导致老年人 WM 损伤。
使用死后磁共振成像（MRI）来描述白质高信号（WMHs）和周围正常表现的白质（NAWM）的病理学。对靶向 WMH 和 NAWM 样本的染色免疫组织化学（IHC）载玻片进行了数字化和量化。WMHs 和 NAWM 与炎症、脱髓鞘和神经胶质增生有关。WMHs 和 NAWM 星形胶质细胞变化包括 AQP1 和 AQP4 表达减少。异常的 NAWM 病理学随着与 WMH 距离的增加而逐渐减轻。
