Heterogeneity of Alzheimer’s disease: Insight from a novel mouse model of amyloid and tau lesions based on the inoculation of human brain preparations
Résumé
Background: A major challenge in clinical research is to better understand the heterogeneity of AD. Indeed, AD is heterogeneous regarding its origin, neuropathology and clinical expressions. While classical sporadic forms of AD (clAD) evolve over approximately 10 years, the "rapidly progressive form of AD" (rAD) is a non-genetic aggressive form associated with a rapid clinical decline that evolves over approximately 2 years (Schmidt et al., Arch Neurol. 2011). Several studies have shown that the experimental inoculation of brain samples with Aβ- and/or tau pathology into transgenic (tg) mouse models overexpressing mutant human APP or tau promotes either Aβ or tau aggregation in the brain of the recipient animal (Gary et al., Acta Neuropathol Com. 2019). The phenotype of the inoculated brains is moreover reproduced in the recipient host (Watts et al., PNAS. 2014). The aim of this work was to study the impact of the inoculations of rAD versus clAD-human brain preparations in tg mice mouse models of β-amyloidosis to explore the mechanisms associated to AD heterogeneity.
Domaines
Neurobiologie
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