|Cortico-Cortical Connectivity: A Key Aspect to Neurodegeneration
The work from William Yang and colleagues (Gu et al., 2005), while directed toward Huntington’s disease (HD), is likely broadly applicable to a number of neurodegenerative disorders including Alzheimer disease (AD). Using two different Cre/LoxP conditional mouse models of HD, these investigators show that restricting mutant huntingtin (mhtt) expression to cortical pyramidal neurons, while capable of forming intracellular aggregates, had no effect on neuropathological hallmarks (reactive gliosis, dysmorphic neuritis, and dark neuron degeneration) nor elicited motor deficits. By marked contrast, expression of mhtt in all of the neurons of the brain resulted in the full spectrum of pathological and motor changes associated with HD. While the issue of whether mhtt expression in pyramidal neurons is necessary for toxicity was not addressed, the overall conclusion that pathological cell-cell interactions are significant contributors to neuronal toxicity in vivo is supported by this and other studies in human...