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Title: Transgenic models of tauopathies and Alzheimer's disease : an investigation into motor learning and recognition memory
Author: Merrick, Georgina
ISNI:       0000 0004 2709 6989
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2010
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The first focus of this thesis was to determine whether motor learning and recognition memory was intact in Line 66+/+ mice, a mouse model which mimics neurodegenerative disease coupled with tau aggregation. Line 66+/+ display positive tau pathology in forebrain, hindbrain and spinal cord by 5 weeks of age. At 4 months of age Line 66+/+ mice were impaired in the motor learning task suggesting that tau pathology had decreased motor performance. Treatment with an anti tau aggregating drug reversed motor learning deficits in Line 66+/+ mice. At 5 months of age Line 66+/+ mice exhibited deficits in the social recognition. This result indicates that transgenic influences on Line 66+/+ mouse performance had extended to social memory function. The second focus of this thesis was investigating recognition memory of a novel triple transgenic model of AD, the PLB1 mouse model. Generation of the PLB1 mouse model came from the realisation that many of current mouse models for AD display major disadvantages in the fact that there is no control for the disturbance caused by the insertion of the transgene(s) with many of them lacking age-specificity, as well as brain-region and cell-type specificity. PLB1Double mice were generated using a knock-in procedure for integration of a single construct containing mutated APP and tau under the control of a forebrain- and age-specific CaMKII promoter. PLB1Double mice were crossed with a PSEN expressing mouse line generating the PLB1Triple line. APP and tau transgenes were flanked by floxed and flirted allowing direct comparison between animals containing one, two or three AD-relevant transgenes. PLB1Triple mice exhibit neuropathological changes by 6 months of age. PLB1mice displayed deficits in behavioural paradigms from 8 months of age suggesting that transgene inclusion had affected recognition of spatial, object and social information.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Alzheimer's disease