Table 3 Animal models of Alzheimer’s disease
Model | FAD / SAD | Genetic mutation | Amyloid plaques | Neurofibrillary tangles | Synaptic impairment | Widespread neurodegeneration | Cognitive impairment | References |
|---|---|---|---|---|---|---|---|---|
5xFAD transgenic mice | FAD | Swedish: APPK670N/M671L Florida: APPI716V London: APPV717I PS1M146L PS1L286V | High levels of intraneuronal Aβ42 beginning at ~ 2 months old Extracellular Aβ deposition begins around 2 months in the subiculum and cortex Plaques are found in the hippocampus and cortex at 6 months Older animals have plaques in the thalamus, brain stem, and olfactory bulb | No | Hippocampus: loss of synapses seen at 12 months | Cortical layer 5, subiculum, and the basal forebrain at 6 months Myelin abnormalities at 6 months of age. Parvalbumin-positive inhibitory interneurons were found in barrel fields of 12 months of age | Spatial memory impairment at 5 months in the Y-maze and 6 months in the water maze Conditioning fear tests impaired at 4 months Olfactory dysfunction at 6 months Motor impairments at 9 months Hearing impairments 14–16 months | [153] |
3x Tg-AD transgenic mice | FAD | Swedish: APPK670N/M671L PS1M146L MAPTP301L | Intracellular Aβ is apparent at 4 months in the neocortex and by 6 months in the CA1 region of the hippocampus Extracellular Aβ deposits in layers 4 and 5 of the frontal cortex and hippocampus are apparent at 6 months | Observed at 18 months in the hippocampus | Occurs at 6 months in the hippocampus | Reduced neurons in the cortex at 11 months and in the CA1 region of the hippocampus in mice 12–15 month old mice | Impairments in retention in retrieval appear at 4 months 6.5 months mice display impairments in learning and memory in Barnes, Y- maze and fear conditioning | [263] |
APP NL-G-F transgenic mice | FAD | Swedish APPK670N/M671L Iberian APPI716F Arctic APPE693G | Plaques develop at 2 months with saturation by 7 months in homozygous mice AB deposition at 4 months in heterozygous mice | No | Yes at 3–4 months and severely impaired at 6–8 months in the CA1 region | No | Memory impairment by 6 months by the Y- maze | [159] |
NFT transgenic mice | N/A | MAPTP301L MAPTP301S | No | Accumulation in cell bodies at 3 months At 9 months the p-tau in the hippocampus resembles early-stage NFT of the human brain | No | Potentially | No | [160] |
Chimeric mice models | FAD | Varies depending on the AD mouse model used | Aβ plaques have been observed in transplanted cells 4 months post-transplantation. | No | Reduction of dendritic staining around human neurons | Transplanted neurons undergo neurodegeneration (4 months post-transplantation), but the murine neurons do not. | Not reported | |
McGill-Thy1-APP rats | FAD | Swedish: APPK670N/M671L Indiana: APPV717F | Extracellular plaques occur at 6 months By 16 months plaques are spread through the hippocampus and the cortex, | Yes | Reduction in synapse density seen at 20 months | Subiculum neuron loss at 22 months | Yes | [264] |
Aged Chimpanzee | SAD | N/A | at ~ 35 years old plaques are found in cortical layers of the prefrontal cortex and medial temporal gyrus and in the CA1 and CA3 regions of hippocampus | at ~ 35 years old NFTs are observed in the CA1 of the hippocampus p-tau and Aβ co-occur in the hippocampus at ~ 35 years. | No | No | Chimpanzees begin to show cognitive decline around 30–45 years old | [265] |
Aged Rhesus monkey | SAD | N/A | In the dorsolateral prefrontal cortex at 33–34 years old | Tau fibrils in the Entorhinal cortex in 24-26-year-old monkey Tau fibrils in pyramidal cells in 38-year-old monkeys p-tau in the dorsolateral prefrontal cortex at 31–34 years | May be induced by Aβ oligomers | In the entorhinal cortex layers at 33–36 years | 26-year-old monkeys exhibit cognitive deficits | [169] |