Lin Wen-Lang, Wszolek Zbigniew K, Dickson Dennis W
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Int J Clin Exp Pathol. 2010 Jul 26;3(7):665-74.
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disorder characterized by cerebral white matter degeneration with myelin loss and axonal swellings (spheroids) leading to progressive cognitive and motor dysfunction. Histopathology of HDLS has been well characterized, but ultrastructural details are lacking. Here we report ultrastructural and immunoelectron microscopic characterization of spheroids and capillary basal lamina in white matter of HDLS brains. Spheroids had thin or discontinuous or no myelin sheaths. They contained various combinations of aggregated neurofilaments (NF), cytoplasmic organelles, dense bodies, and laminated figures. Aggregated filaments labeled with antibodies to phosphorylated NF (pNF), non-pNF and amyloid precursor protein. The gliotic white matter had many reactive astrocytes, and lipid-laden macrophages with membranous and fingerprint-like bodies. The basal laminas (BL) of many capillaries were dilated, and the enlarged space was heavily deposited with banded collagen type I and III. Some BL had focal thickenings and duplications. Fibronectin, not collagen IV, was found associated with banded collagen. The various types of axonal spheroids and changes in capillary basal lamina have not been emphasized previously. It remains to be determined if they are a reactive process or a primary mechanism of white matter degeneration in HDLS.
遗传性弥漫性白质脑病伴球形小体（HDLS）是一种罕见的常染色体显性疾病，其特征为脑白质变性，伴有髓鞘丢失和轴突肿胀（球形小体），导致进行性认知和运动功能障碍。HDLS的组织病理学特征已明确，但超微结构细节尚不清楚。在此，我们报告HDLS脑白质中球形小体和毛细血管基底膜的超微结构及免疫电镜特征。球形小体的髓鞘薄或不连续或无髓鞘。它们包含聚集的神经丝（NF）、细胞质细胞器、致密体和层状结构的各种组合。聚集的细丝用磷酸化NF（pNF）、非pNF和淀粉样前体蛋白抗体标记。胶质增生的白质中有许多反应性星形胶质细胞，以及含有膜状和指纹样小体的富含脂质的巨噬细胞。许多毛细血管的基底膜（BL）扩张，扩大的间隙大量沉积有I型和III型带状胶原。一些BL有局灶性增厚和重复。发现与带状胶原相关的是纤连蛋白，而非IV型胶原。以前未强调过各种类型的轴突球形小体和毛细血管基底膜的变化。它们是HDLS中白质变性的反应性过程还是主要机制仍有待确定。
