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Abstract:
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Despite the clinical heterogeneity among individuals with Down syndrome (DS), the uniformity with which they acquire Alzheimer’s disease (AD) neuropathology as they age makes this population important to study; not only to gain a better understanding of AD, but also because there are currently no effective treatments for DS with AD-like dementia. The pathological links between DS and AD are presumably due to the lifelong overexpression of AD-related genes encoded in chromosome 21, most of them triplicated in DS. The dosage-dependent increase of some of these genes in DS, such as the amyloid precursor protein, leads to plaque formation and further tangle aggregation; changes observed in AD. However, the vast number of chromosome 21 gene products and the complexity of the mechanisms they engender have suggested that they might be giving rise to many diverse neuropathological processes. Recently, the discovery of neuroinflammatory changes in the brains of DS individuals as well as the presence of inflammation-related genes within chromosome 21, prompted the/npossibility that early events in DS patients might be accelerating AD pathogenesis. Until the moment, DS mouse models have provided a powerful tool for translational research, being the Ts65Dn model the most widely used. The possibility that this model might also prove similarly useful in evaluating AD treatments for DS emphasizes the need to study the aging process in the Ts65Dn model. This review also delves into novel therapeutic insight, propounding the pro-inflammatory mediator GSK3 as a/npotential target to rescue AD-like neurodegenerative features in the Ts65Dn DS mouse model. |
