Research Models


Synonyms: APPPS1-21, APP/PS1


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Species: Mouse
Genes: APP, PSEN1
Mutations: APP K670_M671delinsNL (Swedish), PSEN1 L166P
Modification: APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr
Genetic Background: C57BL/6J
Availability: Available through Mathias Jucker


APPPS1 mice contain human transgenes for both APP bearing the Swedish mutation and PSEN1 containing an L166P mutation, both under the control of the Thy1 promoter. In these mice, expression of the human APP transgene is approximately 3-fold higher than endogenous murine APP. Human Aβ42 is preferentially generated over Aβ40, but levels of both increase with age. In the brain, the Aβ42/Aβ40 decreases with the onset of amyloid deposition (Radde et al., 2006; Maia et al., 2013). Amyloid plaque deposition starts at approximately six weeks of age in the neocortex. Deposits appear in the hippocampus at about three to four months, and in the striatum, thalamus, and brainstem at four to five months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.

The CSF levels of Aβ and tau have also been extensively examined in these mice (Maia et al., 2013). Aβ42 concentrations in CSF of these mice decrease with age, with a 50 percent reduction by six months of age and an 80 percent reduction by 18 months. Aβ40 concentrations also decrease, but less dramatically (45 percent by 18 months). CSF concentrations of total tau increase in these animals, starting at six months and reaching a 5-fold increase by 18 months of age. 

The first publication characterizing these mice reported that they exhibited impaired reversal learning of a food-rewarded four-arm spatial maze task at eight months of age (Radde et al., 2006). Others have subsequently reported earlier observations of cognitive impairment, including deficits in the Morris Water maze at seven months of age (Serneels et al., 2009). Impairments in LTP in the hippocampal CA1 region have also been reported to start around this age (Gengler et al., 2010).

Global neuronal loss is not observed in APPPS1 mice, but modest neuron loss was found in the granule cell layer of the dentate gyrus and other subregions with high neuron density at older ages, e.g. 17 months (Rupp et al., 2011).

Modification Details

The human transgenes APP KM670/671NL and PSEN1 L166P are both under the control of the Thy1 promoter. The integration site is on lower arm of chromosome 2 between 40 and 60 cm.

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 begins at 6 weeks of age in the cortex and 3-4 months of age in the hippocampus (Radde et al., 2006).


Phosphorylated tau-positive neuritic processes around plaques have been observed, but no mature tangles (Radde et al., 2006).

Neuronal Loss

Global neuron loss is not observed, but modest neuron loss was found in the granule cell layer of the dentate gyrus and other subregions with high neuronal density in 17-month old animals (Rupp et al., 2011).


Activated microglia around Aβ deposits at 6 weeks as well as increased astrogliosis (Radde et al., 2006). Levels of CCL2 and TNFα increase at later ages (Lee et al., 2010).

Synaptic Loss

Dendritic spine loss around plaques reported to begin approximately 4 weeks after plaque formation and continue for several months (Bittner et al., 2012).

Changes in LTP/LTD

Hippocampal CA1 LTP normal at 4.5 months of age, but impaired at 8 and 15 months of age (Gengler et al., 2010).

Cognitive Impairment

Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months (Serneels et al., 2009). Impaired reversal learning of a food-rewarded four-arm spatial maze task observed at 8 months (Radde et al., 2006).

Last Updated: 09 Jan 2023


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Paper Citations

  1. . Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep. 2006 Sep;7(9):940-6. PubMed.
  2. . Changes in amyloid-β and Tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein. Sci Transl Med. 2013 Jul 17;5(194):194re2. PubMed.
  3. . gamma-Secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer's disease. Science. 2009 May 1;324(5927):639-42. Epub 2009 Mar 19 PubMed.
  4. . Synaptic plasticity in the hippocampus of a APP/PS1 mouse model of Alzheimer's disease is impaired in old but not young mice. PLoS One. 2010;5(3):e9764. PubMed.
  5. . Early onset amyloid lesions lead to severe neuritic abnormalities and local, but not global neuron loss in APPPS1 transgenic mice. Neurobiol Aging. 2011 Dec;32(12):2324.e1-6. PubMed.

Other Citations

  1. Mathias Jucker

Further Reading


  1. . CX3CR1 deficiency alters microglial activation and reduces beta-amyloid deposition in two Alzheimer's disease mouse models. Am J Pathol. 2010 Nov;177(5):2549-62. PubMed.
  2. . Amyloid plaque formation precedes dendritic spine loss. Acta Neuropathol. 2012 Dec;124(6):797-807. PubMed.
  3. . Early Enriched Environment Exposure Protects Spatial Memory and Accelerates Amyloid Plaque Formation in APP(Swe)/PS1(L166P) Mice. PLoS One. 2013;8(7):e69381. PubMed.
  4. . Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2. Mol Neurodegener. 2014 Jun 3;9:20. PubMed.
  5. . Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models. Sci Transl Med. 2015 Oct 14;7(309):309ra164. PubMed.