Outcome of chromosomally normal livebirths with increased fetal nuchal translucency at 10-14 weeks' gestation

Argyrophilic grain disease (AGD) is a distinct degenerative disorder of the human brain associated with the formation of abnormally phosphorylated tau protein. AGD-related cytoskeletal changes are known to affect specific subsets of nerve cells and oligodendrocytes. Here we demonstrate a remarkable association between the apolipoprotein E (ApoE) epsilon2 allele and AGD. Individuals afflicted with AGD (n = 48) reveal a significantly higher frequency of the epsilon2 allele compared with controls (n = 43) (22% versus 4%, P < 0.0002). The association between AGD and epsilon2 allele of ApoE suggests that AGD can be distinguished from other neurodegenerative disorders not only neuropathologically, but also genetically.