Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, USA.
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Acta Neuropathol. 2024 Nov 6;148(1):60. doi: 10.1007/s00401-024-02807-w.
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.
Biondi 小体是神经胶细胞内的丝状淀粉样包涵体,位于脉络丛的室管膜细胞、脑室内的室管膜细胞和脊髓中央管的室管膜细胞中。其形成与年龄有关,常见于多种神经退行性疾病,包括阿尔茨海默病和路易体疾病。在这里,我们发现 Biondi 小体与 TMEM239 强烈免疫反应,TMEM239 是一种针对跨膜蛋白 106B(TMEM106B)包涵体的抗体。Biondi 小体被该抗体和淀粉样染料 pFTAA 标记。许多 Biondi 小体也标记有 TMEM106B 和溶酶体标志物 Hexosaminidase A 和 Cathepsin D。通过透射免疫电子显微镜,脉络丛的 Biondi 小体被 TMEM239 标记,并与类似于残余体或次级溶酶体的结构相关。通过电子冷冻显微镜,脉络丛 Biondi 小体的 TMEM106B 丝与之前在脑实质丝中发现的折叠 I 相似(Biondi 变体),但不完全相同。