Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C. Methods: Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger. Results: Based on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P > .7). Discussion: Our study does not support the role of HDL-C on risk of AD through HDL-C altered by CETP. This study does not rule out other mechanisms by which HDL-C affects risk of AD

Membrane proteins organize a symmetrical virus

Alphaviruses are enveloped icosahedral viruses that mature by budding at the plasma membrane. According to a prevailing model maturation is driven by binding of membrane protein spikes to a preformed nucleocapsid (NC). The T = 4 geometry of the membrane is thought to be imposed by the NC through one-to-one interactions between spike protomers and capsid proteins (CPs). This model is challenged here by a Semliki Forest virus capsid gene mutant. Its CPs cannot assemble into NCs, or its intermediate structures, due to defective CP–CP interactions. Nevertheless, it can use its horizontal spike–spike interactions on membrane surface and vertical spike–CP interactions to make a particle with correct geometry and protein stoichiometry. Thus, our results highlight the direct role of membrane proteins in organizing the icosahedral conformation of alphaviruses