Deposits of amyloid beta protein in the central nervous system of transgenic mice.
Alzheimer's disease is characterized by widespread deposition of amyloid in the central nervous system. The 4-kilodalton amyloid beta protein is derived from a larger amyloid precursor protein and forms amyloid deposits in the brain by an unknown pathological mechanism. Except for aged nonhuman primates, there is no animal model for Alzheimer's disease. Transgenic mice expressing amyloid beta protein in the brain could provide such a model. To investigate this possibility, the 4-kilodalton human amyloid beta protein was expressed under the control of the promoter of the human amyloid precursor protein in two lines of transgenic mice. Amyloid beta protein accumulated in the dendrites of some but not all hippocampal neurons in 1-year-old transgenic mice. Aggregates of the amyloid beta protein formed amyloid-like fibrils that are similar in appearance to those in the brains of patients with Alzheimer's disease.
Wirak
D O
DO
Molecular Therapeutics Inc., Miles Research Center, West Haven, CT 06516.
Bayney
R
R
Ramabhadran
T V
TV
Fracasso
R P
RP
Hart
J T
JT
Hauer
P E
PE
Hsiau
P
P
Pekar
S K
SK
Scangos
G A
GA
Trapp
B D
BD
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000235:genetics; D006624:Hippocampus / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009454:Neurofibrils / Q000648:ultrastructure; D015345:Oligonucleotide Probes; D015183:Restriction Mapping
D016229:Amyloid beta-Peptides; D015345:Oligonucleotide Probes; D004247:DNA