In particular, altered components of the COP9 signalosome have been detected in Smith-Magenis syndrome [29], [31], Down syndrome [33], Alzheimer's disease and Parkinson's disease [34], Machado-Joseph neurodegenerative disease [36], [37], and X-linked mental retardation syndrome [38], [39]. This evidence concerns the gene COPS8 and early-onset autosomal dominant Alzheimer disease.