Abstract #0449

Laukka J, Makki M, Garbern J

Synopsis: Pelizaeus-Merzbacher disease (PMD) is an X-linked leukodystrophy caused by any of a wide variety of mutations affecting proteolipid protein1 (PLP1), the most abundant protein in central nervous system myelin. Severe missense mutations cause oligodendrocyte apoptosis through activation of the unfolded protein response (UPR), which secondary severe hypomyelination. Less severe mutations cause little or no oligodendrocyte apoptosis or hypomyelination, but result in relatively late-onset axonal degeneration. To infer neuropathological changes in PMD, DT-MRI was performed on seven PMD patients with diverse PLP1 mutations and we compared diffusivity and anisotropy of their internal capsules to that of age matched normal control subjects.