Mutations: APP KM670/671NL (Swedish), APP E693G (Arctic)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: Origin: B6D2 F1
These mice express a human APP695 transgene containing the Swedish (K670N/M671L) and Arctic (E693G) mutations, which were introduced by site-directed mutagenesis.
At six months, intracellular punctate deposits of Aβ are abundant in the cortex and hippocampus, but overt β-amyloid plaques are not apparent until 9 to 15 months. Severe cerebral amyloid angiopathy is also present at this age with dense Aβ aggregates in the walls of blood vessels and spreading into the parenchyma (Knobloch et al., 2007).
Cognitive impairment is seen at the age of six months as measured in the Morris water maze and Y-maze (Knobloch et al., 2007).
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Synaptic Loss
Between 9 and 15 months of age β-amyloid plaques became prominent. Plaques had a characteristic dense core morphology which differed from the cotton wool-like structure of plaques seen with the Swedish mutation alone.
- Knobloch M, Konietzko U, Krebs DC, Nitsch RM. Intracellular Abeta and cognitive deficits precede beta-amyloid deposition in transgenic arcAbeta mice. Neurobiol Aging. 2007 Sep;28(9):1297-306. PubMed.
- Vodopivec I, Galichet A, Knobloch M, Bierhaus A, Heizmann CW, Nitsch RM. RAGE does not affect amyloid pathology in transgenic ArcAbeta mice. Neurodegener Dis. 2009;6(5-6):270-80. PubMed.