Research Models




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Species: Mouse
Genes: APP, PSEN1
Mutations: APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M233T, PSEN1 L235P
Modification: APP: Transgenic; PSEN1: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: The PS1KI line was established in 129SV and backcrossed >7 times to C57BL/6 background. The PS1KI were bred with APPSL mice on a C57BL background (two rounds) to obtain a homozygote PS1KI and heterozygote APP.
Availability: Available through Thomas Bayer or Benoit Delatour

Modification Details

This animal is a cross between a PSEN1 knock-in line and an APP over-expressing line. The PS1 knock-in line was generated by introducing two point mutations in the wild-type mouse PSEN1, corresponding to the mutations M233T and L235P. APP751SL overexpresses human APP751 carrying the London (V717I) and Swedish (K670N/M671L) mutations under the control of the Thy1 promoter (Blanchard et al., 2003).


The first signs of Aβ deposition occur in APPSLPS1KI mouse brain at 2.5 months of age compared to six months in APPSL mice. At six months, widespread and numerous round compact Aβ deposits are observed in the cortex, hippocampus, and thalamus, whereas age-matched APPSL mice have very few deposits at this age, restricted mainly to the subiculum and deeper cortical neuronal layers. At ten months, the distribution, density, and size of extracellular Aβ deposits are increased in both models, with similar overall plaque loads. Astrogliosis is observed in parallel with plaque development. The APPSLPS1KI model also develops extensive neuronal loss in the hippocampus and cortex with approximately 33 percent loss of CA1 neurons and 18 percent atrophy of the hippocampus at six months, and 50 percent hippocampal neuron loss at one year of age (Breyhan et al., 2009).


Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at two months, but deficits at six and twelve months compared to PS1KI littermates. Some motor deficits have also been observed (Wirths et al., 2008).

Other Phenotypes

Mice are viable and fertile; however, with age, animals develop decreases in body weight and a spinal deformity (kyphosis) is common (Wirths et al., 2008). Impaired neurogenesis has also been observed (Faure et al., 2011).


Available through Thomas Bayer, Georg-August-Universität Göttingen or Benoit Delatour, ICM, Paris. Requires an agreement from generator at Sanofi.

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.


  • Tangles

No Data


Aβ deposition at 2.5 months compared to 6 months in APPSL mice. At 6 months, numerous compact Aβ deposits in the cortex, hippocampus, and thalamus, whereas in age-matched APPSL mice only very few deposits restricted mainly to the subiculum and deeper cortical layers. At 10 months, deposits increased in distribution, density, and size in both models (Casas et al., 2004).



Neuronal Loss

Some cell loss detectable as early as 6 months in female mice. At 10 months extensive neuronal loss (>50%) is present in the CA1/2 hippocampal pyramidal cell layer. SNeuronal loss also occurs in the frontal cortex and cholinergic system (Casas et al., 2004; Christensen et al., 2008; Christensen et al., 2010).


Astrogliosis occurs in parallel with Aβ deposition, starting around 2.5 months, and in proximity to Aβ-positive neurons (Wirths et al., 2010).

Synaptic Loss

At 6 months, levels of pre- and post-synaptic markers are reduced (Breyhan et al., 2009).

Changes in LTP/LTD

At 6 months there is a large reduction of long-term potentiation and disrupted paired pulse facilitation. No deficit at 4 months (Breyhan et al., 2009).

Cognitive Impairment

Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates (Wirths et al., 2008).

Last Updated: 26 Nov 2013


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Paper Citations

  1. . Time sequence of maturation of dystrophic neurites associated with Abeta deposits in APP/PS1 transgenic mice. Exp Neurol. 2003 Nov;184(1):247-63. PubMed.
  2. . APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy. Acta Neuropathol. 2009 Jun;117(6):677-85. PubMed.
  3. . Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease. Neurobiol Aging. 2008 Jun;29(6):891-901. PubMed.
  4. . Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease. Neurobiol Aging. 2011 Mar;32(3):407-18. PubMed.

Other Citations

  1. Thomas Bayer

Further Reading


  1. . Intracellular Aß triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease. Neurobiol Aging. 2010 Jul;31(7):1153-63. PubMed.
  2. . Transient intraneuronal A beta rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice. Acta Neuropathol. 2008 Dec;116(6):647-55. PubMed.
  3. . Inflammatory changes are tightly associated with neurodegeneration in the brain and spinal cord of the APP/PS1KI mouse model of Alzheimer's disease. Neurobiol Aging. 2010 May;31(5):747-57. PubMed.
  4. . Abundance of Aβ₅-x like immunoreactivity in transgenic 5XFAD, APP/PS1KI and 3xTG mice, sporadic and familial Alzheimer's disease. Mol Neurodegener. 2014 Apr 2;9:13. PubMed.