Transgenic mice expressing APP-C100 in the brain.
The classic hallmarks of Alzheimer's disease are the deposition of amyloid in plaques and in the cerebrovasculature, and the emergence of neurofibrillary tangles in neurons. The interplay between these two pathologic processes, on the one hand, and the degeneration of neurons and loss of cognitive functions on the other, remains incompletely understood. We have proposed that one crucial component of this interplay is a fragment of the Alzheimer amyloid protein precursor (APP) comprising the carboxyterminal 100 amino acids of this molecule, which we term APP-C100 (or, more simply, C100). This fragment, which comprises the 42-amino acid amyloid protein (A beta) and an additional 58 amino acids carboxyterminal to it, was found to be toxic specifically to nerve cells in vitro. We developed transgenic mouse models to test the hypothesis that APP-C100 causes Alzheimer's disease neuropathology. APP-C100 was delivered to the mouse brain via a transgene expressing C100 under the control of the dystrophin brain promoter. These transgenic animal models for the action of APP-C100 in the brain exhibited some of the neuropathological features characteristic of Alzheimer disease brain. The animal models that we have created can be used to test hypotheses concerning the mechanism by which C100 interacts with a neuronal receptor to kill neurons.
Neve
R L
RL
Department of Genetics, Harvard Medical School, Belmont, MA, USA.
Boyce
F M
FM
McPhie
D L
DL
Greenan
J
J
Oster-Granite
M L
ML
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000235:genetics*; D016189:Dystrophin / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics*; D019076:Transgenes / Q000235:genetics
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D016189:Dystrophin