Apolipoprotein E Highly Correlates with AβPP- and Tau-Related Markers in Human Cerebrospinal Fluid

Article type: Research Article

Authors: Vuletic, Simona^a | Li, Ge^b | Peskind, Elaine R.^{b; c} | Kennedy, Hal^a | Marcovina, Santica M.^a | Leverenz, James B.^{b; c; d; e} | Petrie, Eric C.^{b; c} | Lee, Virginia M-Y.^f | Galasko, Douglas^g | Schellenberg, Gerard D.^h | Albers, John J.^{a; *}

Affiliations: [a] Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington School of Medicine, Seattle, WA, USA | [b] Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA | [c] Northwest Network VISN-20 Mental Illness Research, Education and Clinical Center (MIRECC), USA | [d] Parkinson's Disease Research Education and Clinical Center (PADRECC) Northwest (Portland & Seattle), USA | [e] Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA | [f] Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA | [g] Department of Neurosciences, University of California San Diego ADRC, La Jolla, CA, USA | [h] Geriatric Research, Education, and Clinical Center (GRECC); VA Puget Sound Health Care System, Seattle Division, Seattle, WA, USA

Correspondence: [*] Corresponding author: John J. Albers, PhD, University of Washington, Northwest Lipid Metabolism and Diabetes Research Laboratories, 401 Queen Anne Ave N, Seattle, WA 98109, USA. Tel.: +1 206 685 3330; Fax: +1 206 685 3279; E-mail: [email protected].

Abstract: We assessed cerebrospinal fluid (CSF) levels of apolipoprotein E (apoE), phospholipid transfer protein (PLTP) activity, cholesterol, secreted amyloid-β protein precursor α and β (sAβPPα, sAβPPβ), amyloid-β peptides 1–40 (Aβ40) and 1–42 (Aβ42), total tau and tau phosphorylated at threonine 181 (pTau) in neurologically healthy, cognitively intact adults. ApoE significantly correlated with sAβPPα (r = 0.679), sAβPPβ (r = 0.634), Aβ40 (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 sAβPPα (r = 0.292), sAβPPβ (r = 0.281), total and pTau (r = 0.265 and 0.258, respectively; all p ⩽ 0.001). Using partial correlations of CSF biomarkers with apoE, PLTP activity, age and gender, apoE remained significantly correlated with sAβPPα, sAβPPβ, Aβ40, total and pTau (p < 0.001). The presence of apoE ε2 was associated with lower levels of apoE, PLTP activity and Aβ42, while APOEε4 had no significant impact on any of the measured variables. Our data suggest that there is a significant physiological link between apoE and AβPP, as well as between apoE and tau in neurologically healthy, cognitively intact individuals.

Keywords: Amyloid-β, amyloid-β protein precursor protein, apolipoprotein E, cerebrospinal fluid, phospholipid transfer protein, tau

DOI: 10.3233/JAD-2008-15307

Journal: Journal of Alzheimer's Disease, vol. 15, no. 3, pp. 409-417, 2008