Inter-Species Glia Differences: Implications for Successful Translation of Transgenic Rodent Alzheimer's Disease...

Despite a multitude of efficacious treatments for the cognitive symptoms and pathology in transgenic mouse models of Alzheimer's disease (AD), success in human trials has been elusive. Rodent-human brain dissimilarities may help explain failures of past human trials and improve outcomes of future ones. This review highlights the essential role of the human brain's exceptional myelination in achieving and maintaining optimal brain functions, as well as underlying its vulnerability to age-related myelin breakdown and the degenerative brain diseases that process can trigger. This alternative myelin-centered perspective is used herein to help explain key disconnects in the existing treatment literature by focusing on recent reports on brain effects of bexarotene, the only marketed retinoid X receptor (RXR) agonist. The myelin perspective exposes significant yet underexplored opportunities for novel treatment and prevention interventions that have the potential to considerably reduce the tremendous burden of degenerative brain diseases.