Autosomal Dominant Leukodystrophy (ADLD), a fatal adult onset demyelinating 
disorder, is the only human disease that has been linked to mutations of the 
nuclear lamina protein, lamin B1, and is primarily caused by duplications of the 
LMNB1 gene. Why CNS myelin is specifically targeted and the mechanisms 
underlying ADLD are unclear. Recent work from our group has demonstrated that 
over expression of lamin B1 in oligodendrocytes, the myelin producing cells in 
the CNS, resulted in age dependent epigenetic modifications, transcriptional 
down-regulation of lipogenic gene expression and significant reductions of 
myelin-enriched lipids. Given the high lipid content of meylin, we hypothesize 
that lipid loss is one of the primary drivers of the demyelination phenotype. 
These results can, at least partially, explain the age dependence and cell type 
specificity in ADLD and are discussed in the context of the existing literature, 
in an attempt to delineate potential pathways underlying the disease phenotype.