Differences in the Aβ40/Aβ42 ratio associated with cerebrospinal fluid lipoproteins as a function of apolipoprotein E genotype

The ε4 allele of apolipoprotein E (ApoE) is a risk factor for Alzheimer's disease (AD). ApoE, which is important for lipid metabolism, is also a major constituent of cerebrospinal-fluid (CSF) lipoproteins (LPs). Although 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-β (Aβ) protein may normally be associated with CSF LPs. It is converted in AD to 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 ApoE genotype. Interestingly, plasma and CSF high-density lipoprotein (HDL) cholesterol and apolipoprotein AI (ApoAI) levels were correlated. Importantly, as assessed by size-exclusion chromatography, Aβ in CSF coeluted in fractions containing LPs and was influenced by ApoE genotype: E4-positive subjects displayed significant elevations in Aβ40/Aβ42 ratios. These results suggest that plasma ApoAI/HDL levels can influence CSF ApoAI/HDL levels and that interactions between Aβ and central nervous system LPs may reflect changes in brain Aβ metabolism before the onset of clinical disease.