|Budget Amount *help
¥2,700,000 (Direct Cost : ¥2,700,000)
Fiscal Year 1999 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1998 : ¥1,600,000 (Direct Cost : ¥1,600,000)
Neuropathological studies of patients with Niemann-Pick disease type C (NPC) have revealed neurofibrillary tangles (NFT) in cases showing slowly progressive chronic courses. However, no NFT have been noted in NPC patients younger that 20 years, and it is known that long-term perturbation of neuronal cellular metabolism for 10 years or more may result in NFT formatiion.
Mice with NPC, which shows autosomal recessive inheritance, develop hepatosplenomegaly and neurological manifestations such as ataxia and tremor, and die at about 14 weeks of age. This is not comparable with the time scale of NFT positive NPC in humans. Here we examined murine NPC (spm/spm) neuropathologically, using LFB-Bodian staining , electron microscopy and immunohistochemistry with anti Alzheimer's neurofibrillary tangle (ANT, Ab39) antibody, in order to investigate Alzheimer's neurofibrillary changes.
Neurofibrillary changes resembling NFT can be seen microscopically in neuranal cells of cerebral cortex, hippocampal gyrus and midbrain older at 11 and 13-week old spm/spm by LBF-Bodian staining and by immunostaining with commercially available anti-PHF-tau. However, only neuron from neocortex can be staind with anti ANT (Ab39) antibody. Equally, paired helical filaments only can be seen in the neuron of neocortex. The present findings of NFT-like structure in the neocortex of murine NPC may provide an animal model for elucidating the pathogenesis of Alzheimer's disease. We also tried to establish the neuronal cell culture from the brain of newborn spm, but have not been successful yet.