Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of Niemann-Pick C disease

The BALB/c mouse model of Niemann-Pick type C (NPC) disease exhibits neurop athological similarities to the human condition. There is an age-related ce rebral atrophy, demyelination of the corpus callosum, and degeneration of c erebellar Purkinje cells in the NPC mouse. In human NPC, many cortical and subcortical neurons contain neurofibrillary tangles, which are thought by s ome investigators to play an important role in the neurodegenerative proces s. The purpose of the present study was to determine whether neurodegenerat ion occurs in the NPC mouse, in brain regions other than the cerebellum and whether the degeneration is related to the presence of neurofibrillary tan gles. Using light microscopic methods with immunohistochemistry, electron m icroscopy, and cell counting methods, 11-week-old NPC+/+ and NPC-/- animals were examined. In the NPC-/- mice, there were 96% fewer Purkinje cells, 28 % fewer neurons in the prefrontal cortex, 20% fewer neurons in the thalamus , and 63% fewer glial cells in the corpus callosum. On the other hand, prev ious studies indicate normal numbers of neurons and glial cells in these sa me neuroanatomical regions in young NPC-/- mice. There were normal numbers of cholinergic neurons in sections assessed in the striatum and basal foreb rain in the Ii-week-old animals and no evidence of neurofibrillary tangles within cells. The present data indicate that both neurons and glial cells d ie in the NPC mouse but that all cells are not equally vulnerable. There wa s no evidence for neurofibrillary tangles in the NPC mouse, and therefore t he degenerative process in the mouse is unrelated to the neurofibrillary ta ngle. (C) 2001 Wiley-Liss, Inc.