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Wingo TS, Cutler DJ, Wingo AP, Le NA, Rabinovici GD, Miller BL, Lah JJ, Levey AI. Association of Early-Onset Alzheimer Disease With Elevated Low-Density Lipoprotein Cholesterol Levels and Rare Genetic Coding Variants of APOB. JAMA Neurol. 2019 Jul 1;76(7):809-817. PubMed.
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Comments
It makes a lot of sense to look at early onset cases for potential genetic associations because early onset is clearly more strongly “genetic.” If we better understood how these variants work mechanistically, we might be able to design prevention or treatment.
It’s good that Wingo and colleagues were able to assemble so many EOAD cases, however, I have some concerns about their choice of controls and how different the controls were from the cases they assembled. ApoE and ApoB variants likely have associations with survival and, of course, a lot of people as they age are being treated with lipid-lowering drugs which would affect that relationship. There may be a lot more to be learned about this association in my judgment.
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