Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation

被引：317

作者：

De-Hua Chui ^{[1
]}

Hiroshi Tanahashi ^{[1
]}

Kazuharu Ozawa ^{[2
]}

Sachiya Ikeda ^{[2
]}

Frédéric Checler ^{[3
]}

Otoya Ueda ^{[2
]}

Hiroshi Suzuki ^{[2
]}

Wataru Araki ^{[1
]}

Haruhisa Inoue ^{[1
]}

Keiro Shirotani ^{[1
]}

Keikichi Takahashi ^{[1
]}

Ferenc Gallyas ^{[4
]}

Takeshi Tabira ^{[1
]}

机构：

[1] National Institute of Neuroscience,Department of Demyelinating Disease and Aging

[2] NCNP,Department of Neurosurgery

[3] Fuji Gotemba Research Labs,undefined

[4] Chugai Pharmaceutical,undefined

[5] Institut de Pharmacologie Moléculaire et Cellulaire,undefined

[6] CNRS,undefined

[7] University Medical School of Pécs,undefined

来源：

Nature Medicine | 1999年 / 5卷 / 5期

关键词：

D O I：

10.1038/8438

中图分类号：

学科分类号：

摘要：

Familial Alzheimer disease mutations of presenilin 1 (PS-1) enhance the generation of Aβ1–42, indicating that PS-1 is involved in amyloidogenesis. However, PS-1 transgenic mice have failed to show amyloid plaques in their brains. Because PS-1 mutations facilitate apoptotic neuronal death in vitro , we did careful quantitative studies in PS-1 transgenic mice and found that neurodegeneration was significantly accelerated in mice older than 13 months (aged mice) with familial Alzheimer disease mutant PS-1, without amyloid plaque formation. However, there were significantly more neurons containing intracellularly deposited Aβ42 in aged mutant transgenic mice. Our data indicate that the pathogenic role of the PS-1 mutation is upstream of the amyloid cascade.

引用

页码：560 / 564

页数：4