Research Models


Synonyms: APP/PS1, APPswe/PS1deltaE9, line 85, APP(swe) + PSEN1DeltaE9, APdE9


Back to the Top

Species: Mouse
Genes: APP, PSEN1
Mutations: APP KM670/671NL (Swedish), PSEN1: deltaE9
Modification: APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Genetic Background: C57BL/6 x C3H)F2
Availability: The Jackson Lab; available through the JAX MMRRC Stock# 034829; Live


These transgenic mice were made by co-injecting two vectors encoding mutant APP and mutant PSEN1. Like the APPSwe/PSEN1dE9 mice generated by crossing transgenic APP animals with those expressing PSEN1dE9, these mice begin to develop Aβ deposits by 6 months of age, with abundant plaques in the hippocampus and cortex by 9 months (Jankowsky et al., 2004). Plaques continue to increase up to around 12 months of age (Garcia-Alloza et al., 2006). Astrocytosis develops in parallel with plaque deposition, with severe gliosis starting around 6 months, especially in the vicinity of plaques. The number of GFAP-positive cells progressively increases with age, with extensive staining throughout the cortex by 15 months (Kamphuis et al., 2012). Tangles are not typical in these animals.

In the congenic line (see related strains below), differences between male and female mice have been reported with regard to the kinetics of plaque deposition in the brain and plasma Aβ levels. In females, levels of Aβ in the plasma increase about 80 percent between ages of 3 and 15 months, whereas levels reportedly decrease about 40 percent in males over that time, such that by 15 months of age plasma Aβ40 was about fourfold higher in females than in males. A similar trend was seen for Aβ42, although the difference was smaller. In the brain, no sex-related differences in Aβ levels were observed between the ages of 1 and 15 months. In terms of amyloid deposition, males developed plaques more rapidly than females, reaching saturation at 9 months of age, whereas deposition did not plateau in females until around 12 months of age (Ordóñez-Gutiérrez et al., 2014).

The behavior of these animals has been well characterized. They have impaired spatial learning by 12 months as measured by the Morris water maze, specifically during acquisition of the hidden platform sub-task and the probe trial, but not in the visible platform test (Lalonde et al., 2005). They have been shown to commit more errors than wild-type mice in the Morris water maze at 13 months, but not at 7 months (Volianskis et al., 2008).

These mice have a high incidence of spontaneous epileptic seizures, including generalized seizures, as detected by video-EEG. Seizures start at a young age and are present in about 65 percent of APPswe/PSEN1dE9 mice by 4.5 months of age, but are not observed in littermate controls. Seizures are lethal in only about 5 percent of mice, depending on breeding conditions (Minkeviciene et al. 2009).

Deficits in synaptic plasticity have been observed. Specifically, deficits in transient long-term potentiation (t-LTP) have been observed by 3 months, although the degree of impairment is not related to age from 3 to 12 months (Volianskis et al., 2008).

In addition to cognitive, behavioral, and neurological phenotypes, bladder dysfunction has been reported in the congenic line (see related strains below). This phenotype has been observed in both males and females, although with differing ages of onset. Bladder dysfunction was observed in males from a young age, whereas females do not develop the phenotype until around 10 months of age (Ordóñez-Gutiérrez et al., 2014).

This strain does not carry the retinal degeneration allele Pde6brd1.

This model was formerly available through The Jackson Lab as Stock# 004462.

Modification Details

These transgenic mice were made by co-injecting two vectors encoding mutant APP and mutant PSEN1. The APP sequence encodes a chimeric mouse/human APP (Mo/HuAPP695swe) that was “humanized” by modifying three amino acids, and the Swedish mutation was introduced. The PSEN1 sequence encodes human presenilin 1 lacking exon 9 (dE9), which therefore models AD-associated mutations in PSEN1 resulting in exclusion of exon 9, variously known as ΔE9, dE9, deltaE9, Δ9, or delE9. Expression of both genes was directed to the CNS with the mouse prion promoter.

Related Strains

Backcrossed onto a C57 background for at least eight generations. Available through the JAX MMRRC Stock# 034832 (formerly The Jackson Lab Stock# 005864).

Phenotype Timeline

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



  • Tangles


  • Neuronal Loss
  • Synaptic Loss


Occasional Aβ deposits can be found by 6 months with abundant plaques in the hippocampus and cortex by 9 months (Jankowsky et al., 2004) and a progressive increase in plaques up to 12 months (Garcia-Alloza et al., 2006).



Neuronal Loss



Minimal astrocytosis at 3 months; significant astrocytosis by 6 months, especially in areas around plaques. Extensive GFAP+ staining at 15 months and later throughout the cortex (Kamphuis et al., 2012).

Synaptic Loss


Changes in LTP/LTD

Transient long term potentiation (t-LTP) is reduced by 3 months. The degree of impairment is not related to age from 3 to 12 months (Volianskis et al., 2008).

Cognitive Impairment

Impairment in the Morris water maze at 12 months, specifically during acquisition of the hidden platform sub-task and the probe trial but not in the visible platform test (Lalonde et al., 2005). At 13 months the mice commit more errors in the Morris water maze, but not at 7 months (Volianskis et al., 2008).



No Available Comments

Make a comment or submit a question

To make a comment you must login or register.


Research Models Citations

  1. APPSwe/PSEN1dE9

Paper Citations

  1. . Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet. 2004 Jan 15;13(2):159-70. Epub 2003 Nov 25 PubMed.
  2. . Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis. 2006 Dec;24(3):516-24. Epub 2006 Oct 5 PubMed.
  3. . GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease. PLoS One. 2012;7(8):e42823. Epub 2012 Aug 13 PubMed.
  4. . Peripheral Amyloid Levels Present Gender Differences Associated with Aging in AβPP/PS1 Mice. J Alzheimers Dis. 2015 Jan 1;44(4):1063-8. PubMed.
  5. . Exploratory activity and spatial learning in 12-month-old APP(695)SWE/co+PS1/DeltaE9 mice with amyloid plaques. Neurosci Lett. 2005 Dec 23;390(2):87-92. PubMed.
  6. . Episodic memory deficits are not related to altered glutamatergic synaptic transmission and plasticity in the CA1 hippocampus of the APPswe/PS1δE9-deleted transgenic mice model of ß-amyloidosis. Neurobiol Aging. 2010 Jul;31(7):1173-87. Epub 2008 Sep 13 PubMed.
  7. . Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci. 2009 Mar 18;29(11):3453-62. PubMed.

External Citations

  1. JAX MMRRC Stock# 034832
  2. JAX MMRRC Stock# 034829

Further Reading


  1. . Activation of neurotensin receptor 1 facilitates neuronal excitability and spatial learning and memory in the entorhinal cortex: beneficial actions in an Alzheimer's disease model. J Neurosci. 2014 May 14;34(20):7027-42. PubMed.
  2. . Reductions in endocannabinoid levels and enhanced coupling of cannabinoid receptors in the striatum are accompanied by cognitive impairments in the AβPPswe/PS1ΔE9 mouse model of Alzheimer's disease. J Alzheimers Dis. 2014;42(1):227-45. PubMed.
  3. . Longitudinal follow-up of autophagy and inflammation in brain of APPswePS1dE9 transgenic mice. J Neuroinflammation. 2014 Aug 27;11:139. PubMed.