C. Czech et al., PROTEOLYTICAL PROCESSING OF MUTATED HUMAN AMYLOID PRECURSOR PROTEIN IN TRANSGENIC MICE, Molecular brain research, 47(1-2), 1997, pp. 108-116
The evidence that beta A4 is central to the pathology of Alzheimer's d
isease (AD) came from the identification of several missense mutations
in the amyloid precursor protein (APP) gene co-segregating with famil
ial AD (FAD). In an attempt to study the proteolytical processing of m
utated human APP in vivo, we have created transgenic mice expressing t
he human APP695 isoform with four FAD-linked mutations. Expression of
the transgene was controlled by the promoter of the HMG-CR gene. Human
APP is expressed in the brain of transgenic mice as shown by Western
blot and immunohistology. The proteolytic processing of human APP in t
he transgenic mice leads to the generation of C-terminal APP fragments
as well as to the release of beta A4. Despite substantial amounts of
beta A4 detected in the brain of the transgenic mice, neither signs of
Alzheimer's disease-related pathology nor related behavioural deficit
s could be demonstrated.