T41B (Thy1-hAPPLond/Swe+ [Line 41])
Alzheimer’s disease (AD), the most common cause of dementia, is an age dependent progressive neuro-degenerative disorder. Amyloid-beta (a metabolic product of amyloid precursor protein; APP) plays an important role in pathology of AD. APP may also be important in synaptic plasticity and learning and memory processes in the hippocampus. The line 41 of mThy1-hAPPLond/swe mouse (hAPP751+) is a transgenic mouse model of AD expressing high level of human APP751 cDNA containing the London (V717I) and Swedish (K670M/N671L) mutations under the regulatory control of the murine (m)Thy-1 gene. Six month old male mThy1-APPLond/Swe mice show hyperactivity, learning and memory deficit, and social interaction abnormalities. This transgenic line shows mature amyloid-beta plaques, pathological hallmarks of AD, in the frontal cortex as early as 3-4 months of age and develop plaques in the hippocampus, thalamus, olfactory region, basolateral amygdala, and Subiculum at the age of 5-7 months.
The Thy1-APPLond/Swe+ line presents well-established cognitive deficits, mature β-amyloid plaques, and synaptic degeneration in various brain regions. Transgenic (Tg) subjects show deficits in spatial working memory, as assessed by T- and Y-Maze Spontaneous Alternation tasks (A) and Delayed-Match-To-Place (DMP) Dry Maze task (B). Tg mice do not show deficits in acquisition or tone-cued memory retrieval, but show significant contextual memory retrieval impairment (C). Tg subjects are hyperactive in a novel environments (D). Tg mice show deficit in 3-chamber social novelty test(E). Quantification of β-amyloid in Hippocampal CA3, Basolateral amygdala, and Subiculum (F).