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Neurolipidomics: an inflammatory perspective on fat in the brain.

The apolipoprotein E (APOE) gene is an important pathogenic determinant in several neurologic diseases, including Alzheimer disease, traumatic brain injury, multiple sclerosis, and possibly HIV-associated dementia, depending on the individual APOE allele. The mechanisms by which different APOE alleles influence susceptibility to neurologic disease remain uncertain, but clearly the epsilon 4 (E4) allele confers a greater risk of neurologic disease. Several mechanistic possibilities include the differential effects of APOE alleles on neurite outgrowth; though other potential APOE-mediated effects include promoting the efflux of free cholesterol from macrophages, thereby influencing the risk of vascular disease and the regulation of oxidative/nitrosative stress in neural cells. Indeed, APOE is regarded as an acute phase/inflammatory protein that might act as a chaperone in the formation of cleaved pathogenic proteins such as s-amyloid. In …