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Int J Clin Exp Pathol 2010;3(7):665-674
Hereditary diffuse leukoencephalopathy with spheroids: ultrastructural and
immunoelectron microscopic studies
Wen-Lang Lin, Zbigniew K. Wszolek, Dennis W. Dickson
Departments of 1Neuroscience and 2Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA
Received July 19, 2010; accepted July 23, 2010; available online July 26, 2010
Abstract: 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. (IJCEP1007008).
Keywords: hereditary diffuse leukoencephalopathy, spheroids, capillary basal lamina, ultrastructure, immunoelectron microscopy
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Address all correspondence to:
Dennis W. Dickson, M.D.
Robert E. Jacoby Professor of Alzheimer's Research
4500 San Pablo Road
Jacksonville, FL 32224 USA