PDF(Pubmed)
Abstract：
BACKGROUND: TAR DNA-Binding Protein 43 (TDP-43) pathological inclusions are a distinctive feature in dozens of neurodegenerative pathologies, including limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Prior investigations identified vascular-associated TDP-43-positive micro-lesions, known as \"Lin bodies,\" located on or near the brain capillaries of some individuals with LATE-NC. This study aimed to investigate the relationship between the accumulation of Lin bodies and glial cells in LATE-NC and the potential co-localization with ferritin, a protein associated with iron storage. Using multiplexed immunohistochemistry and digital pathology tools, we conducted pathological analyses to investigate the relationship between Lin bodies and glial markers (GFAP for astrocytes, IBA1 for microglia) and ferritin. Analyses were conducted on post-mortem brain tissues collected from individuals with pathologically confirmed Alzheimer\'s disease neuropathological changes (ADNC) and LATE-NC.
RESULTS: As shown previously, there was a robust association between Lin bodies and GFAP-positive astrocyte processes. Moreover, we also observed Lin bodies frequently co-localizing with ferritin, suggesting a potential link to compromised vascular integrity. Subsequent analyses demonstrated increased astrocytosis near Lin body-positive vessels compared to those without Lin bodies, particularly in ADNC cases. These results suggest that the accumulation of Lin bodies may elicit an increased glial response, particularly among astrocytes, possibly related to impaired vascular integrity.
CONCLUSIONS: Lin bodies are associated with a local reactive glial response. The strong association of Lin bodies with ferritin suggests that the loss of vascular integrity may be either a cause or a consequence of the pTDP-43 pathology. The reactive glia surrounding the affected vessels could further compromise vascular function.
RESULTS: As shown previously, there was a robust association between Lin bodies and GFAP-positive astrocyte processes. Moreover, we also observed Lin bodies frequently co-localizing with ferritin, suggesting a potential link to compromised vascular integrity. Subsequent analyses demonstrated increased astrocytosis near Lin body-positive vessels compared to those without Lin bodies, particularly in ADNC cases. These results suggest that the accumulation of Lin bodies may elicit an increased glial response, particularly among astrocytes, possibly related to impaired vascular integrity.
CONCLUSIONS: Lin bodies are associated with a local reactive glial response. The strong association of Lin bodies with ferritin suggests that the loss of vascular integrity may be either a cause or a consequence of the pTDP-43 pathology. The reactive glia surrounding the affected vessels could further compromise vascular function.
摘要：
背景：TARDNA结合蛋白43（TDP-43）病理包涵体是数十种神经退行性病变的显着特征，包括边缘占优势的年龄相关的TDP-43脑病神经病理变化（LATE-NC）。先前的研究确定了血管相关的TDP-43阳性微病变，被称为“林的尸体，位于某些患有LATE-NC的人的脑毛细血管上或附近。本研究旨在探讨LATE-NC中Lin体和胶质细胞的积累与铁蛋白的潜在共定位之间的关系。一种与铁储存有关的蛋白质。使用多重免疫组织化学和数字病理学工具，我们进行了病理学分析，以研究Lin体与神经胶质标志物之间的关系（星形胶质细胞的GFAP，IBA1表示小胶质细胞）和铁蛋白。对从病理证实为阿尔茨海默病神经病理学改变（ADNC）和LATE-NC的个体收集的死后脑组织进行分析。
结果：如前所述，Lin体与GFAP阳性星形胶质细胞过程之间存在显著关联.此外，我们还观察到Lin身体经常与铁蛋白共同定位，提示血管完整性受损的潜在联系。随后的分析表明，与没有林体的血管相比，林体阳性血管附近的星形细胞增多，特别是在ADNC的情况下。这些结果表明，林体的积累可能会引起神经胶质反应增加，特别是在星形胶质细胞中，可能与血管完整性受损有关。
结论：Lin体与局部反应性神经胶质反应有关。Lin体与铁蛋白的强烈关联表明血管完整性的丧失可能是pTDP-43病理的原因或结果。受影响血管周围的反应性神经胶质可能进一步损害血管功能。
结果：如前所述，Lin体与GFAP阳性星形胶质细胞过程之间存在显著关联.此外，我们还观察到Lin身体经常与铁蛋白共同定位，提示血管完整性受损的潜在联系。随后的分析表明，与没有林体的血管相比，林体阳性血管附近的星形细胞增多，特别是在ADNC的情况下。这些结果表明，林体的积累可能会引起神经胶质反应增加，特别是在星形胶质细胞中，可能与血管完整性受损有关。
结论：Lin体与局部反应性神经胶质反应有关。Lin体与铁蛋白的强烈关联表明血管完整性的丧失可能是pTDP-43病理的原因或结果。受影响血管周围的反应性神经胶质可能进一步损害血管功能。
