Mutations: APP KM670/671NL (Swedish)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57BL/6J
Availability: Available through Lars Nilsson
Transgene with human APP (isoform 695) bearing the Swedish mutation under the murine Thy1 promoter.
Extracellular amyloid deposition begins at approximately 12 months (Philipsson et al., 2009) whereas intraneuronal Aβ aggregates occur at approximately 6 months (Lord et al., 2006). Extracellular pathology, both cerebrovascular amyloid angiopathy (CAA) and congophilic parenchymal plaques, are mainly found in the cerebral cortex, hippocampus and thalamus. Aβ-burden in cerebral cortex is approximately 1 percent at 12 months and 2.8 percent at 18 months (Lord et al., 2011).
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Neuronal Loss
- Synaptic Loss
- Changes in LTP/LTD
- Cognitive Impairment
Plaques are detectable at approximately 12 months and are heterogeneous in morphological structure and size, as well as in terms of fluorescence emitted when stained with luminescent polymers (conformational amyloid ligands)(Philipsson et al., 2009).
Microgliosis and astrogliosis are most prominent in the hippocampus, but also found locally around deposits in the cerebral cortex and in thalamus at approximately 12 months (Philipsson et al., 2009).
Changes in LTP/LTD
Research Models Citations
- Philipson O, Hammarström P, Nilsson KP, Portelius E, Olofsson T, Ingelsson M, Hyman BT, Blennow K, Lannfelt L, Kalimo H, Nilsson LN. A highly insoluble state of Abeta similar to that of Alzheimer's disease brain is found in Arctic APP transgenic mice. Neurobiol Aging. 2009 Sep;30(9):1393-405. PubMed.
- Lord A, Kalimo H, Eckman C, Zhang XQ, Lannfelt L, Nilsson LN. The Arctic Alzheimer mutation facilitates early intraneuronal Abeta aggregation and senile plaque formation in transgenic mice. Neurobiol Aging. 2006 Jan;27(1):67-77. PubMed.
- Lord A, Philipson O, Klingstedt T, Westermark G, Hammarström P, Nilsson KP, Nilsson LN. Observations in APP bitransgenic mice suggest that diffuse and compact plaques form via independent processes in Alzheimer's disease. Am J Pathol. 2011 May;178(5):2286-98. PubMed.
No Available Further Reading