Research Models


Synonyms: Truncated beta-amyloid 42


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Species: Mouse
Genes: APP
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57BL6
Availability: Available through Thomas Bayer.


The TBA42 model was designed to produce and secrete an N-terminally truncated Aβ peptide. TBA42, which stands for truncated beta-amyloid 42, specifically encodes an Aβ3–42 peptide with a glutamine substituted for the naturally occurring glutamate at position 3 of Aβ in order to facilitate pyroglutamate formation in vivo. Pyroglutamate Aβ3–42 (AβpE3–42) is a modified Aβ peptide that is enriched in the AD brain. It is derived from Aβ42, from which the first two amino acids are removed, and the resulting free amino group is converted to a cyclic amide by the enzyme glutaminyl cyclase. This creates a highly stable, neurotoxic form of Aβ that aggregates faster than conventional full-length Aβ42. In addition, pyroglutamate Aβ has been identified as a major component of Aβ plaques (Saido et al., 1995; Harigaya et al., 2000). The strategy used to generate this model enables the effects of this specific Aβ species to be assessed while avoiding the potential confounds of over-expressing APP.

TBA42 mice exhibit intraneuronal accumulation of Aβ in the hippocampus by three months and in cerebellar nuclei by six months. Amyloid plaques are only very rarely detected, but marked gliosis in the hippocampus occurs by 12 months.

Behaviorally, the mice exhibit select age-dependent deficits, including a deficit in working memory as assessed by the cross maze at 12 months, but not at three and six months. They also have an early and persistent decrease in anxiety as measured by the elevated plus maze. General motor coordination is comparable to wild-type mice at three and six months as indicated by the balance beam test, but impairments are observed at 12 months.

When crossed with the 5xFAD model, the resulting progeny, known as FAD42 mice, have an aggravated behavioral phenotype compared with either 5xFAD or TBA42 alone. Specifically, FAD42 mice have greater motor impairment on the balance beam and reduced anxiety in the elevated plus maze (Wittnam et al., 2012).

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
  • Changes in LTP/LTD


Very rare extracellular Aβ deposits at all ages tested.



Neuronal Loss



Marked gliosis in the hippocampus as measured by GFAP staining at 12 months.

Synaptic Loss


Changes in LTP/LTD


Cognitive Impairment

Age-dependent behavioral deficits, including working memory as assessed by the cross maze at 12 months, but not at 3 and 6 months.


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  1. The TBA42 model produces human pyroglutamate Aβ3-42 in the CA1 region of the hippocampus. This peptide has received considerable attention in recent years, and has been hypothesized to be the Aβ species that seeds toxic aggregates, having prion-like features. The TBA42 model specifically expresses N-truncated human Aβ3-42 fused to a thyrotropin-releasing hormone backbone. Because these animals express no human APP, the effects of pyroglutamate Aβ3-42 are not confounded by other human APP products, such as sAPPα, sAPPβ, p3, and C-terminal fragments, which have a variety of biological activities, including neurotrophic and synaptotrophic effects. Another advantage to the TBA42 model is that it does not develop a severe plaque load. (Plaque levels do not correlate with cognitive decline in AD patients).


Research Models Citations

  1. 5xFAD

Paper Citations

  1. . Dominant and differential deposition of distinct beta-amyloid peptide species, A beta N3(pE), in senile plaques. Neuron. 1995 Feb;14(2):457-66. PubMed.
  2. . Amyloid beta protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain. Biochem Biophys Res Commun. 2000 Sep 24;276(2):422-7. PubMed.
  3. . Pyroglutamate amyloid β (Aβ) aggravates behavioral deficits in transgenic amyloid mouse model for Alzheimer disease. J Biol Chem. 2012 Mar 9;287(11):8154-62. PubMed.

Other Citations

  1. Thomas Bayer

Further Reading


  1. . Shotgun brain proteomics reveals early molecular signature in presymptomatic mouse model of Alzheimer's disease. J Alzheimers Dis. 2013 Jan 1;37(2):297-308. PubMed.