Research Models


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

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, respectively. Like the APPSwe/PSEN1dE9 mice generated by crossing transgenic APP animals with those expressing PSEN1dE9, these mice begin to develop Aβ deposits by six months of age, with abundant plaques in the hippocampus and cortex by nine 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 six 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). Between eight and 10 months, modest neuronal loss was observed adjacent to plaques relative to more distal areas (Jackson et al., 2016). Tangles are not typical in these animals.

The behavior of these mice has been well-characterized. Deficits have been reported across cognitive domains, although severity and timing depend on the specific behavioral protocols used (Janus et al., 2015). Contextual memory may be impaired as early as six months of age, as shown by freezing behavior in fear-conditioning tests (Kilgore et al., 2010). Spatial learning is comparable to non-Tg mice at seven months of age, but impaired by 12 months as measured by performance in the Morris water maze (Lalonde et al., 2005; Volianskis et al., 2010). Spontaneous behavior, such as nest-building and burrowing, is also affected (Janus et al., 2015).

Deficits in synaptic plasticity have been observed. Specifically, deficits in transient long-term potentiation (t-LTP) have been observed by three months, although the degree of impairment is not related to age from three to 12 months (Volianskis et al., 2010).

The hybrid line has a relatively high incidence of spontaneous epileptic seizures. Seizures start at a young age and are present in about 65 percent of APPswe/PSEN1dE9 mice by 4.5 months of age. Seizures are lethal in only about 5 percent of mice, depending on breeding conditions (Minkeviciene et al., 2009). Other genetic backgrounds, especially the D2 background, are even more prone to seizures (see related strains below).

APPswe/PSEN1dE9 mice have been made on several genetic backgrounds (see related strains below). In the B6 congenic line, differences between male and female mice have been reported. For example, in females, plasma Aβ levels increase about 80 percent between three and 15 months of age, to fourfold higher in females by 15 months of age, whereas levels decrease in males over that time. A similar trend was seen for Aβ42. Males develop amyloid plaques more rapidly than females, saturating at nine months of age, whereas plaque deposition does not plateau in females until around 12 months of age (Ordóñez-Gutiérrez et al., 2015). Studies using the B6 congenic line have also shown increased complement protein in the brain. Specifically, complement protein C1q was greater in the hippocampus of APPswe/PSEN1dE9 mice than in non-Tg controls at four months of age. Additionally, there was greater co-localization of C3 protein and PSD-95 puncta (Hong et al., 2016).

Bladder dysfunction has been reported in B6 congenic APPswe/PSEN1dE9 mice. Males are affected from a young age, whereas females do not develop bladder dysfunction until around 10 months of age (Ordóñez-Gutiérrez et al., 2015).

The hybrid line does not carry the retinal degeneration allele Pde6brd1. It 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. In addition, the mutations necessary for the Swedish mutation were 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 protein promoter.

Related Strains

(aka C57BL/6J APPswePsen1de9 and B6.APBTg)
These mice are on a congenic C57/BL genetic background. They are available as JAX MMRRC Stock# 034832 (formerly as Jackson Lab Stock# 005864).

D2.APBTg mice
These mice are on a D2 genetic background. They were generated by backcrossing B6.APBTg mice to stock D2 mice (DBA/2J; JAX Stock #000671). Mice on this background are more prone to spontaneous seizures than the B6 congenic. The seizures are lethal, and are thought to account for the premature death of D2.ABPTg mice; 70 percent die between two and three months of age. Those that survive to six months of age exhibit reduced amyloid pathology relative to B6 counterparts (Jackson et al., 2015).

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

Neuronal Loss

Neuronal loss observed adjacent to plaques relative to more distal areas.


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).


Not observed.


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

In the B6 congenic mice, age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and Homer immunoreactivity in the hippocampus by 4 months (Hong et al., 2016).

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).



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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. . Human tau increases amyloid β plaque size but not amyloid β-mediated synapse loss in a novel mouse model of Alzheimer's disease. Eur J Neurosci. 2016 Dec;44(12):3056-3066. Epub 2016 Nov 12 PubMed.
  5. . Behavioral abnormalities in APPSwe/PS1dE9 mouse model of AD-like pathology: comparative analysis across multiple behavioral domains. Neurobiol Aging. 2015 Sep;36(9):2519-32. Epub 2015 May 21 PubMed.
  6. . Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology. 2010 Mar;35(4):870-80. PubMed.
  7. . 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.
  8. . 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.
  9. . Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci. 2009 Mar 18;29(11):3453-62. PubMed.
  10. . Peripheral amyloid levels present gender differences associated with aging in AβPP/PS1 mice. J Alzheimers Dis. 2015;44(4):1063-8. PubMed.
  11. . Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science. 2016 May 6;352(6286):712-6. Epub 2016 Mar 31 PubMed.
  12. . DBA/2J genetic background exacerbates spontaneous lethal seizures but lessens amyloid deposition in a mouse model of Alzheimer's disease. PLoS One. 2015;10(5):e0125897. Epub 2015 May 1 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.
  4. . Behavioral and neuropathological consequences of transient global ischemia in APP/PS1 Alzheimer model mice. Behav Brain Res. 2014 Dec 15;275:15-26. Epub 2014 Sep 1 PubMed.