AD-EDMD associated missense mutations in the LMNA gene are thought to result in misfolding of the protein or the failure to assemble into lamin A polymers [39], and Krimm et al. have shown that the substitution of arginine 453 by tryptophan causes a dramatic reduction of the denaturation temperature of the Ig-fold domain due to the loss of a salt bridge between R453 and E443/E444 [11]. This evidence concerns the gene LMNA and Alzheimer disease.