Revisiting rodent models: Octodon degus as Alzheimer’s disease model?

Abstract

Alzheimer’s disease primarily occurs as sporadic disease and is accompanied with vast socio-economic problems. The mandatory basic research relies on robust and reliable disease models to overcome increasing incidence and emerging social challenges. Rodent models are most efficient, versatile, and predominantly used in research. However, only highly artificial and mostly genetically modified models are available. As these ‘engineered’ models reproduce only isolated features, researchers demand more suitable models of sporadic neurodegenerative diseases. One very promising animal model was the South American rodent Octodon degus, which was repeatedly described as natural ‘sporadic Alzheimer’s disease model’ with ‘Alzheimer’s disease-like neuropathology’. To unveil advantages over the ‘artificial’ mouse models, we re-evaluated the age-dependent, neurohistological changes in young and aged Octodon degus (1 to 5-years-old) bred in a wild-type colony in Germany. In our hands, extensive neuropathological analyses of young and aged animals revealed normal age-related cortical changes without obvious signs for extensive degeneration as seen in patients with dementia. Neither significant neuronal loss nor enhanced microglial activation were observed in aged animals. Silver impregnation methods, conventional, and immunohistological stains as well as biochemical fractionations revealed neither amyloid accumulation nor tangle formation. Phosphoepitope-specific antibodies against tau species displayed similar intraneuronal reactivity in both, young and aged Octodon degus.In contrast to previous results, our study suggests that Octodon degus born and bred in captivity do not inevitably develop cortical amyloidosis, tangle formation or neuronal loss as seen in Alzheimer’s disease patients or transgenic disease models.

Lack of spontaneous age-related brain pathology in Octodon degus: a reappraisal of the model

“…Altogether these data suggest that no AD-related pathology can be found in aged octodons, in conflict with previous reports567, but in accordance with a more recent contribution8.…”

“…Overall, our investigation has not unveiled any specific pattern of age-related pathology therefore questioning the relevance of such rodent as a natural model for age-related disorders. Interestingly, a recent study came to the same conclusions with the same groups of age while focusing on AD-related pathology8. Although the common max life expectancy is 3–4 years in the wild, captivity allows prolonged life span up to 5–8 years, thus suggesting that our age-groups are relevant for the study of age-related phenomenons817.…”

“…Interestingly, Ardiles and collaborators described that most age-related changes occurred between 12 and 36 months5. However, most of these deficits could not be identified in our cohort as well as in, a recently published independent study that also failed to identify AD-related brain pathology8.…”

“…This rodent presents an interesting homology with human amyloid-β (Aβ) sequence differing in only one amino-acid8, a feature similarly displayed by α-syn with a 96% predicted sequence homology (96%) compared to human sequence (Supp. Table 1).…”

Alzheimer’s disease: experimental models and reality

“…Some studies have found that Octodon degu have intracellular and extracellular accumulation of Aβ, plaques at old ages, intracellular tau accumulation, astrocytosis, synaptic changes and memory impairment that correlates with increased levels of oligomers (reviewed in [16, 131]). However this pathology appears to be inconsistent as other studies do report any AD associated pathology in aged animals [149]. …”