Collins HM, Greenfield S (2024) Rodent models of alzheimer’s disease: Past misconceptions and future prospects. Int J Mol Sci 25(11):6222. doi: 10.3390/ijms25116222 PMID: 38892408
Objective: To outline the various apparent causes of Alzheimer’s Disease (AD) and evaluate the success or otherwise of their reproduction in rodents.
Summary: To understand the pathogenesis of AD and how it progresses through the brain, the authors describe the need of an animal model that reproduces the causal mechanism driving the disease. For decades, researchers have attempted to model AD by recapitulating downstream markers of its pathology, including cholinergic neuron loss, Aβ and tau aggregation, and neuroinflammation. Insights gained from the study of Parkinson’s Disease (PD) show that we must model the actual neurodegenerative mechanisms of AD in adult, wildtype animals by specifically targeting the neural populations first affected by a disease. The authors propose an alternative model, based on the aberrant accumulation of the novel peptide T14. In the review, specific cholinergic neuron degeneration was produced by 192 IgG-saporin, which resulted in degeneration of cholinergic cell bodies and terminals via apoptotic cell death.
See Also:
- Book AA et al. 192 IgG-saporin: I. Specific lethality for cholinergic neurons in the basal forebrain of the rat. J Neuropathol Exp Neurol 53:95-102, 1994.
- McGaughy J et al. The role of cortical cholinergic afferent projections in cognition: impact of new selective immunotoxins. Behav Brain Res 115:251-263, 2000.
- Holley LA et al. Cortical cholinergic deafferentation following the intracortical infusion of 192-IgG-saporin: a quantitative histochemical study. Brain Res 663:277-286, 1994.