Age-dependent phenotypic characteristics of a triple transgenic mouse model of Alzheimer disease.
Behavioral Neuroscience. 2008-01-01; 122(4): 733-747
DOI: 10.1037/a0012520
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Pietropaolo S(1), Feldon J, Yee BK.
Author information:
(1)Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology
Zurich, Schwerzenbach, Switzerland.
The triple-transgenic mouse line (3 x Tg-AD) harboring PS1M146V, APPSwe, and
taup301L transgenes represents the only transgenic model for Alzheimer’s disease
(AD) to date capturing both beta-amyloid and tau neuropathology. The present
study provides an extensive behavioral characterization of the 3 x Tg-AD mouse
line, evaluating the emergence of noncognitive and cognitive AD-like symptoms at
two ages corresponding to the early (6-7 months) and advanced (12-13 months)
stages of AD-pathology. Enhanced responsiveness to aversive stimulation was
detected in mutant mice at both ages: the 3 x Tg-AD genotype enhanced acoustic
startle response and facilitated performance in the cued-version of the water
maze. These noncognitive phenotypes were accompanied by hyperactivity and
reduced locomotor habituation in the open field at the older age. Signs of
cognitive aberrations were also detected at both ages, but they were limited to
associative learning. The present study suggests that this popular transgenic
mouse model of AD has clear phenotypes beyond the cognitive domain, and their
potential relationship to the cognitive phenotypes should be further explored.