Bouter Y, Dietrich K, Wittnam JL, Rezaei-Ghaleh N, Pillot T, Papot-Couturier S, Lefebvre T, Sprenger F, Wirths O, Zweckstetter M, Bayer TA. N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits. Acta Neuropathol. 2013 Aug;126(2):189-205. PubMed.

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  1. The Tg4-42 model is the first, and currently only, model to express N-truncated human Aβ4-42 without any other mutation, yet still develop neuronal loss and behavioral deficits. This is unique, because all other transgenic models that develop these pathologies have at least one mutation. Likewise, the TBA42 model, which has glutamine in place of glutamate at position three of Aβ, develops similar pathologies while expressing otherwise wild-type Aβ. The Tg4-42 model has very clear hippocampal pathology with severe age-dependent neuron loss, as determined by stereology, and it exhibits age-dependent cognitive decline.

    Researchers interested in the molecular network of the hippocampus and its molecular signature related to AD might find this model of interest. It is known that APP and its proteolytic products, such as sAPPα, sAPPβ, p3, and C-terminal fragments, have biological effects, including neurotrophic and synaptothrophic effects. Because the Tg4-42 model expresses only human Aβ4-42, the effects of this peptide can be studied without interference from other human APP products. Another advantage is that this model does not develop plaques, which are not correlated with cognitive decline in AD patients.

    A major problem with APP transgenic models of AD is that they depend on mutant APP expression. Each mutation has a particular effect on Aβ production. It could very well be that these models only reflect a subset of AD patients. It is now well-recognized that N-truncated Aβ species (including 4-42) are abundant in the AD brain, including in sporadic cases, but they are rare in most APP transgenic mice.

    View all comments by Thomas Bayer

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