Contributed by Stefania Forner, PhD
Most cases of Alzheimer’s disease (AD) are late-onset and occur sporadically; however, the majority of AD animal models are based on rare genetic mutations, making them good models of the less common familial AD, which accounts for 1% of all cases. As treatments effective in these mouse models have proven ineffective in humans, there is a clear need to develop new models that better represent the more common, late-onset sporadic form of AD.
With this in mind, my colleagues and I at UCI MIND used a different approach in a recent study published in Nature Communications. Using genetic engineering, we developed a new model that expresses beta amyloid that more closely mirrors its human counterpart. This model, commonly named hAβ-KI, can be considered a “platform model” for the study of late-onset AD.
While the hAβ-KI mice do not display the more advanced brain plaques and tangles linked with the disease, they do present impairments in cognition and synaptic plasticity, decreases in brain volume, and other changes in the brain that are associated with late-onset AD in humans.
The hAβ-KI mouse model is an important foundation of the NIH-established consortium, MODEL-AD, and will serve as a platform for researchers to identify key factors that drive late-onset AD and to produce novel and improved models, with the ultimate goal of improving prevention and treatment in humans.
Dr. Stefania Forner is the Project Manager/Scientist of the NIH MODEL-AD Consortium at UCI. Dr. Forner completed a postdoctoral training with Dr. Frank LaFerla at UCI MIND where she investigated the impact of intra and extracellular beta-amyloid in synaptic loss and neuroinflammation in Alzheimer’s Disease.
