Acta Neuropathologica ( IF 9.3 ) Pub Date : 2024-11-06 , DOI: 10.1007/s00401-024-02807-w Bernardino Ghetti, Manuel Schweighauser, Max H. Jacobsen, Derrick Gray, Mehtap Bacioglu, Alexey G. Murzin, Bradley S. Glazier, Taxiarchis Katsinelos, Ruben Vidal, Kathy L. Newell, Sujuan Gao, Holly J. Garringer, Maria Grazia Spillantini, Sjors H. W. Scheres, Michel Goedert
Biondi bodies are filamentous amyloid inclusions of unknown composition in ependymal cells of the choroid plexuses, ependymal cells lining cerebral ventricles and ependymal cells of the central canal of the spinal cord. Their formation is age-dependent and they are commonly associated with a variety of neurodegenerative conditions, including Alzheimer’s disease and Lewy body disorders. Here, we show that Biondi bodies are strongly immunoreactive with TMEM239, an antibody specific for inclusions of transmembrane protein 106B (TMEM106B). Biondi bodies were labelled by both this antibody and the amyloid dye pFTAA. Many Biondi bodies were also labelled for TMEM106B and the lysosomal markers Hexosaminidase A and Cathepsin D. By transmission immuno-electron microscopy, Biondi bodies of choroid plexuses were decorated by TMEM239 and were associated with structures that resembled residual bodies or secondary lysosomes. By electron cryo-microscopy, TMEM106B filaments from Biondi bodies of choroid plexuses were similar (Biondi variant), but not identical, to the fold I that was previously identified in filaments from brain parenchyma.
中文翻译:
室管膜细胞 Biondi 小体中的淀粉样蛋白丝TMEM106B
Biondi 小体是脉络丛室管膜细胞、脑室内膜细胞和脊髓中央管管管膜细胞中成分未知的丝状淀粉样蛋白包涵体。它们的形成与年龄有关,通常与各种神经退行性疾病有关,包括阿尔茨海默病和路易体疾病。在这里,我们表明 Biondi 小体与 TMEM239 具有很强的免疫反应性, 是一种对跨膜蛋白 106B (TMEM106B) 包涵体具有特异性的抗体。Biondi 小体由该抗体和淀粉样蛋白染料 pFTAA 标记。许多 Biondi 小体也被标记为 TMEM106B以及溶酶体标志物己糖胺酶 A 和组织蛋白酶 D。通过透射免疫电子显微镜检查,脉络丛的 Biondi 小体被 TMEM239 修饰,并与类似于残余小体或次级溶酶体的结构相关联。通过电子冷冻显微镜,来自脉络丛 Biondi 小体的 TMEM106B 丝与先前在脑实质细丝中鉴定的折叠 I 相似(Biondi 变体),但不相同。