Alzheimer’s Disease Models

Model Summary

Tg2576 mice, acquired from Taconic Biosciences, are one of the most extensively used and well-characterized models of Alzheimer’s disease. This Alzheimer’s mouse model, created on a B6:SJL mixed background, carries the Swedish mutation (KM670/671NL) driven by the hamster prion protein promoter (Prnp), which causes overexpression of APP695, resulting in increased levels of amyloid-beta and amyloid plaque formation. Tg2576 transgenic mice have been reported to exhibit cognitive deficits at 6-8 months of age, gliosis at 9 months, and amyloid plaques at 12 months. This Alzheimer’s disease research model does not exhibit neurofibrillary tangles or neuronal loss.

Validation Data

Tg2576 transgenic mice carrying mutations related to Alzheimer’s disease have reduced cognitive function. A) Both the mutant mice (orange line) and normal mice (red line) learned the initial location of the hidden platform. B) The transgenic mice (orange bars), though, did not remember the target quadrant 4 and 24 hours after the last training trial, while normal mice did (red bars). C) During reversal learning, normal mice were trained to the new quadrant (red line), but the mouse model of Alzheimer's failed (orange line). Data sets that do not share any letters differed significantly. (n.s.= not significant).

Amyloid-beta was detected in perfusion fixed, paraffin embedded sections of brains (A) from female and male wildtype (WT) and Tg2576 (Tg) mice. Amyloid (brown spots) was quantified in the cortex (B) and hippocampus (C) of the brain slices. 

Model Summary

5XFAD transgenic mice, acquired from The Jackson Laboratory and licensed through Northwestern University, are a specific model of Alzheimer's disease that carry mutations in human amyloid precursor protein and presenilin 1 genes associated with Familial Alzheimer's Disease. Available on both a C57BL/6J background and on a B6:SJL mixed background, these mice overexpress both human amyloid precursor protein with the Swedish (KM670/671NL), Florida (I716V), and London (V717I) Familiar Alzheimer's Disease mutations and human presenilin 1 harboring two Familiar Alzheimer's Disease mutations, M146L and L286V. These mutations, driven by the mouse Thy1 promoter, contribute to an accelerated intraneuronal amyloid plaque accumulation, gliosis, and reduced synaptic markers, along with behavioral deficits mimicking Alzheimer’s disease. These mutant mice do not exhibit neurofibrillary tangles.

Model Summary

ARTE10 mice, created on a C57BL/6NTac background, comprises two co-integrated constructs in mice. Specifically, it involves expression of a transgene encoding the 695-amino acid isoform with the Swedish mutation of the human amyloid precursor protein (KM670/671NL), and another construct carrying human presenilin 1 with the M146V mutation (PS1M146V). The co-inheritance of these transgenes is governed by the Thy1 promoter, allowing for streamlined breeding with other mouse models. This Alzheimer's animal model, acquired from Taconic Biosciences, have been reported to develop amyloid plaques at 3 months of age, followed by neuronal loss, gliosis at 6 months, and cognitive impairments at 12 months of age. ARTE10 mice do not exhibit neurofibrillary tangles. 

Validation Data

Tau, phosphorylated at residues Ser202/Thr205 (brown), was detected in the hippocampus of a 12-month-old ARTE10 mouse. The mouse brain tissue was counterstained with H&E.

Amyloid plaques (brown) were detected in a perfusion-fixed brain from a 12-month-old ARTE10 model of Alzheimer's disease.

Model Summary

JNPL3 transgenic mice, acquired from Taconic Biosciences, express a mutant form of human tau protein associated with neurofibrillary tangles. This mutant tau, featuring the four-repeat tau isoform (4R0N) with the P301L mutation, is regulated by the mouse Prnp promoter. The P301L mutation contributes to tau pathology and the formation of neurofibrillary tangles. JNPL3 mice develop neurofibrillary tangles at 4-6 months, and gliosis and neuronal loss at about 10 months of age. This in vivo model for Alzheimer’s does not form amyloid plaques.

Model Summary

APPSWE-Tau mice, acquired from Taconic Biosciences, are produced through the mating of Tg2576 mice, which carry the Swedish mutation (KM670/671NL) of human amyloid precursor protein, and JNPL3 mice, which express the four-repeat tau isoform (4R0N) with the P301L mutation. These transgenic mice exhibit neurofibrillary tangles and gliosis at about 3 months of age, and amyloid plaques at 9 months. There are no reports of APPSWE-Tau mice displaying synaptic loss or cognitive impairments.

Model Summary

Tau P301S (PS19) transgenic mice from The Jackson Laboratory express a human tau protein with the disease associated P301S mutation and that is under the control of the mouse Prnp promoter. These models of Alzheimer's disease exhibit gliosis at 3 months of age, followed by synaptic loss at 3-6 months, and neurofibrillary tangles and cognitive impairments at about 6 months. There are no reports of Tau P301S (PS19) mouse models displaying amyloid plaques.

Our pre-developed transgenic rat models express genetic mutations associated with Alzheimer’s disease and provide a valuable platform to study Alzheimer’s disease mechanisms, test therapeutic interventions, and bridge the translational gap between preclinical findings and potential human treatments.

• ApoE knockout rat
• human ApoE2 knockin rat
• human ApoE3 knockin rat

• human ApoE4 knockin rat
• App knockout rat
• BDNF knockout rat