To reimagine existing preclinical trials for Alzheimer's disease, University of Pittsburgh School of Medicine neuroscientists created the first non-human primate model of hereditary Alzheimer's in marmoset monkeys, outlining their approach in Alzheimer's & Dementia: Translational Research & Clinical Interventions.
Marmoset models bridge the current translation gap between human studies and cell and rodent models of AD. Establishment of marmoset models of aging and genetic risk loci for AD will enable robust and reliable mapping of cognitive and molecular outcomes across species. AD, Alzheimer's disease.
If allowed to age naturally, marmosets will spontaneously develop aggregates of toxic amyloid beta and tau indicative of Alzheimer's-like pathology in the brain. To create marmosets with inheritable predisposition to Alzheimer's disease, researchers introduced a series of mutations in the PSEN1 gene using the Crispr/Cas9 gene engineering system. These same mutations cause early onset Alzheimer's disease in humans.
Presenilin-1, the protein encoded by PSEN1, plays a key role in generating amyloid tangles, and, just like, marmosets with a mutation in the PSEN1 gene start developing Alzheimer's-like pathologies during adolescence. In establishing the model, the team is applying a bench-to-bedside approach to marmosets as though they were human patients.
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