Apolipoprotein E highly correlates with AbetaPP- and tau-related markers in human cerebrospinal fluid

Abstract

We assessed cerebrospinal fluid (CSF) levels of apolipoprotein E (apoE), phospholipid transfer protein (PLTP) activity, cholesterol, secreted amyloid-beta protein precursor alpha and beta (sAbetaPPalpha, sAbetaPPbeta), amyloid-beta peptides 1-40 (Abeta_{40}) and 1-42 (Abeta_{42}), total tau and tau phosphorylated at threonine 181 (pTau) in neurologically healthy, cognitively intact adults. ApoE significantly correlated with sAbetaPPalpha (r = 0.679), sAbetaPPbeta (r = 0.634), Abeta_{40} (r = 0.609), total and pTau (r = 0.589 and r = 0.673, respectively, all p < 0.001), PLTP activity (r = 0.242, p = 0.002) and cholesterol (r = 0.194, p < 0.01). PLTP activity significantly correlated with sAbetaPPalpha (r = 0.292), sAbetaPPbeta (r = 0.281), total and pTau (r = 0.265 and 0.258, respectively; all p <or= 0.001). Using partial correlations of CSF biomarkers with apoE, PLTP activity, age and gender, apoE remained significantly correlated with sAbetaPPalpha, sAbetaPPbeta, Abeta_{40}, total and pTau (p < 0.001). The presence of apoE epsilon2 was associated with lower levels of apoE, PLTP activity and Abeta_{42}, while APOEepsilon4} had no significant impact on any of the measured variables. Our data suggest that there is a significant physiological link between apoE and AbetaPP, as well as between apoE and tau in neurologically healthy, cognitively intact individuals.