Differences in the A beta 40/A beta 42 ratio associated with cerebrospinalfluid lipoproteins as a function of apolipoprotein E genotype

The epsilon 4 allele of apolipoprotein E (ApoE) is a risk factor for Alzhei mer's disease (AD). ApoE, which is important for lipid metabolism, is also a major constituent of cerebrospinal fluid (CSF) lipoproteins (LPs). Althou gh ApoE in the CSF is derived from the central nervous system, the relation between LP metabolism in plasma and CSF is not clear. Soluble amyloid-P (A P) protein may normally be associated with CSF LPs. It is converted in AD t o a fibrillar form in brain parenchyma. ApoE and CSF LPs may regulate this process. The purpose of this study was to characterize CSF LPs from healthy , cognitively normal, fasted, elderly individuals at different risk for AD based on ApoE genotype, Lipid composition of CSF LPs did not differ with Ap oE genotype. Interestingly, plasma and CSF high-density lipoprotein (HDL) c holesterol and apolipoprotein AI (ApoAI) levels were correlated. Importantl y, as assessed by size-exclusion chromatography, A beta in CSF coeluted in fractions containing LPs and was influenced by ApoE genotype: E4-positive s ubjects displayed significant elevations in A beta 40/A beta 42 ratios. The se results suggest that plasma ApoAI/HDL levels can influence CSF ApoAI/HDL levels and that interactions between AP and central nervous system LPs may reflect changes in brain A beta metabolism before the onset of clinical di sease.