Nihon Shinkei Seishin Yakurigaku Zasshi Japanese Journal of Psychopharmacology, May 1, 2007
Alzheimer&amp... more Alzheimer's disease is characterized by progressive loss of cognitive function due to amyloid-l (Al) deposits in the central nervous system. Based on the amyloid cascade theory, many reports indicated that immunotherapy is effective for the treatment of Alzheimer's disease. We developed a mucosal immunotherapy for Alzheimer's disease via oral vaccine with recombinant adeno-associated virus (AAV) vector and nasal administration of recombinant sendaivirus vector expressing Al 1-43/IL-10. Oral or nasal administration of recombinant virus vector induced the long-term expression of All in the epithelial cells and presented the Ap antigen to the mucosal immune system. Antibody levels in the mouse serum were elevated after 4 weeks and the antibody inhibited the aggregation of Ap in vitro. Immunohistochemistry of the APP transgenic mouse brain tissue showed that All burdens were markedly decreased in the treated mouse compared to the control. The inflammation was not recognized in any organ including brain and kidney. Mucosal immunotherapy with viral vectors significantly cleared the Ap depositions without inflammation and reduced the levels of Al in the brain homogenates of APP transgenic mice; therefore, it might be effective for the treatment of Alzheimer's disease.
This is an abstract of my lecture on familial non-Alzheimer dementia. 1. Vascular dementia 1) Cer... more This is an abstract of my lecture on familial non-Alzheimer dementia. 1. Vascular dementia 1) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by autosomal dominant inheritance, smooth muscle cell degeneration and granular osmiophilic material (GOM) in arterioles, and Notch 3 mutations. 2) CARASIL This is an autosomal recessive vascular dementia with unknown etiology. 3) Familial amyloid angiopathy Familial cerebral hemorrhage and dementia is caused by mutations in amyloid precursor protein, cystatin c, and Bri genes. 2. Familial non-Alzheimer degenerative dementia 1) Dementia with Lewy bodies This is characterized by Alzheimer like dementia, visual hallucination and diffuse Lewy bodies which are formed by ubiquitinated alpha-synuclein. Occasionally, familial forms are reported, but gene mutations are unknown. 2) Frontotemporal dementia (FTD) FTDP-17 is characterized by tau mutations, character and personal changes, and disinhibition. The gene mutations were also found in familial forms of Pick's disease, corticobasal degeneration, and other tauopathies. 3) Familial British dementia (FBD), familial Danish dementia (FDD) FBD and FDD are characterized by Abri amyloid deposits, amyloid angiopathy and dementia. Mutations in Bri gene are reported. 4) Familial encephalopathy with neuroserpin inclusion bodies (FENIB) FENIB is characterized by dementia, Collins body and neuroserpin gene mutation.
Nihon Shinkei Seishin Yakurigaku Zasshi Japanese Journal of Psychopharmacology, May 1, 2007
Alzheimer&amp... more Alzheimer's disease is characterized by progressive loss of cognitive function due to amyloid-l (Al) deposits in the central nervous system. Based on the amyloid cascade theory, many reports indicated that immunotherapy is effective for the treatment of Alzheimer's disease. We developed a mucosal immunotherapy for Alzheimer's disease via oral vaccine with recombinant adeno-associated virus (AAV) vector and nasal administration of recombinant sendaivirus vector expressing Al 1-43/IL-10. Oral or nasal administration of recombinant virus vector induced the long-term expression of All in the epithelial cells and presented the Ap antigen to the mucosal immune system. Antibody levels in the mouse serum were elevated after 4 weeks and the antibody inhibited the aggregation of Ap in vitro. Immunohistochemistry of the APP transgenic mouse brain tissue showed that All burdens were markedly decreased in the treated mouse compared to the control. The inflammation was not recognized in any organ including brain and kidney. Mucosal immunotherapy with viral vectors significantly cleared the Ap depositions without inflammation and reduced the levels of Al in the brain homogenates of APP transgenic mice; therefore, it might be effective for the treatment of Alzheimer's disease.
This is an abstract of my lecture on familial non-Alzheimer dementia. 1. Vascular dementia 1) Cer... more This is an abstract of my lecture on familial non-Alzheimer dementia. 1. Vascular dementia 1) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by autosomal dominant inheritance, smooth muscle cell degeneration and granular osmiophilic material (GOM) in arterioles, and Notch 3 mutations. 2) CARASIL This is an autosomal recessive vascular dementia with unknown etiology. 3) Familial amyloid angiopathy Familial cerebral hemorrhage and dementia is caused by mutations in amyloid precursor protein, cystatin c, and Bri genes. 2. Familial non-Alzheimer degenerative dementia 1) Dementia with Lewy bodies This is characterized by Alzheimer like dementia, visual hallucination and diffuse Lewy bodies which are formed by ubiquitinated alpha-synuclein. Occasionally, familial forms are reported, but gene mutations are unknown. 2) Frontotemporal dementia (FTD) FTDP-17 is characterized by tau mutations, character and personal changes, and disinhibition. The gene mutations were also found in familial forms of Pick's disease, corticobasal degeneration, and other tauopathies. 3) Familial British dementia (FBD), familial Danish dementia (FDD) FBD and FDD are characterized by Abri amyloid deposits, amyloid angiopathy and dementia. Mutations in Bri gene are reported. 4) Familial encephalopathy with neuroserpin inclusion bodies (FENIB) FENIB is characterized by dementia, Collins body and neuroserpin gene mutation.
Uploads
Papers by Takeshi Tabira