Plasma signaling proteins in persons at genetic risk for Alzheimer disease: influence of APOE genotype.

ABSTRACT: To study the effect of familial Alzheimer disease (FAD) mutations and APOE genotype on plasma signaling protein levels.Cross-sectional comparison of plasma levels of 77 proteins measured using multiplex immune assays.A tertiary referral dementia research center.Thirty-three persons from families harboring PSEN1 or APP mutations, aged 19 to 59 years.Protein levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs) and among APOE genotype groups, using multiple linear regression models.Twenty-one participants were FAD MCs and 12 were NCs. Six had the APOE ?2/3, 6 had the ?3/4, and 21 had the ?3/3 genotype. Levels of 17 proteins differed among APOE genotype groups, and there were significant interactions between age and APOE genotype for 12 proteins. Plasma levels of apolipoprotein E and superoxide dismutase 1 were highest in the ?2 carriers, lowest in ?4 carriers, and intermediate in the ?3 carriers. Levels of multiple interleukins showed the opposite pattern and, among the ?4 carriers, demonstrated significant negative correlations with age. Although there were no significant differences between FAD MCs and NCs, there were interactions between mutation status and APOE genotype for 13 proteins.We found different patterns of inflammatory markers in young and middle-aged persons among APOE genotype groups. The APOE ?4 carriers had the lowest levels of apolipoprotein E. Young ?4 carriers have increased inflammatory markers that diminish with age. We demonstrated altered inflammatory responses in young and middle adulthood in ?4 carriers that may relate to AD risk later in life.

SUBMITTER: Ringman JM 

PROVIDER: S-EPMC3668092 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature