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Title: Investigations of age- and plaque-related learning deficits in PDAPP mice and evaluations of anti-amyloidosis strategies on amyloid precursor protein transgenic mice
Author: Chen, Guiquan
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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A cross-sectional and a longitudinal design were employed to address whether PDAPP mice exhibit any plaque-related learning deficit. Firstly, the cross-sectional study indicated that PDAPP mice simultaneously displayed an early (plaque-independent) and age-related learning impairment. Further analysis showed that the age-related learning deficit was highly correlated with plaque burden in the hippocampus of aged PDAPP mice, suggesting that amyloid plaques play a very important role in memory loss of AD. Second, the longitudinal study showed that the same PDAPP mice exhibited significant age-related learning deficits in trials to criterion and learning capacity tasks when they aged. Interestingly, cued navigation and object recognition in both cross-sectional and longitudinal studies were unaffected, indicating normal sensorimotor function and recognition memory of PDAPP mice. The longitudinal study further showed that the age-related learning impairment was significantly correlated with significantly reduced size of field potentials, suggesting important roles of amyloid plaques in disturbing synaptic transmission and cognitive function. Preclinical data indicated that Aβ immunotherapy is very effective to improve both AD-like neuropathology and cognitive impairment in APP transgenic mice. Using active Aβ immunisation, long-term (9 months: prevention study) and short-term (5 months: treatment study) effects of Aβ vaccines (AN-1792) on synaptic transmission and spatial learning of PDAPP mice were investigated. Although neither of the two studies showed that Aβ vaccines had significant improvement on either synaptic transmission or spatial learning of PDAPP mice, both long-term and short-term Aβ vaccinations effectively reduced the levels of total Aβ. Thus, these two studies indicated that active Aβ immunotherapy might be very effective to improve AD-like pathology, but ineffective to rescue the learning impairment in APP mice.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available