Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration

被引:109
作者
Higuchi, M
Ishihara, T
Zhang, B
Hong, M
Andreadis, A
Trojanowski, JQ
Lee, VMY [1 ]
机构
[1] Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA
[2] Eunice Kennedy Shriver Ctr Mental Retardat Inc, Dept Biomed Sci, Waltham, MA 02254 USA
关键词
D O I
10.1016/S0896-6273(02)00789-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Frontotemporal dementias (FTDs), including cortico-basal degeneration (CBD) and progressive supranuclear palsy (PSP), are neurodegenerative tauopathies characterized by widespread CNS neuronal and glial tau pathologies, but there are no tau transgenic (Tg) mice that model neurodegeneration with glia tau lesions. Thus, we generated Tg mice overexpressing human tau in neurons and glia. No neuronal tau aggregates were detected, but old mice developed Thioflavin S- and Gallyas-positive glial tau pathology resembling CBD astrocytic plaques. Tau-immunoreactive and Gallyas-positive oligodendroglial coiled bodies (similar to CBD and PSP), glial degeneration, and motor deficits were associated with age-dependent accumulations of insoluble hyperphosphorylated human tau and tau immunopositive filaments in degenerating glial cells. Thus, tau-positive glial lesions similar to human FTDs occur in these Tg mice, and these pathologies are linked to glial and axonal degeneration.
引用
收藏
页码:433 / 446
页数:14
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