RT Journal
A1 Ringman JM, Elashoff D, Geschwind DH, et al
T1 Plasma signaling proteins in persons at genetic risk for alzheimer disease: Influence of apoe genotype
JF Archives of Neurology
JO Archives of Neurology
YR 2012
FD June 1
VO 69
IS 6
SP 757
OP 764
DO 10.1001/archneurol.2012.277
UL http://dx.doi.org/10.1001/archneurol.2012.277
AB Objective 
                  To study the effect of familial Alzheimer disease (FAD) mutations and APOE genotype on plasma signaling protein levels.Design 
                  Cross-sectional comparison of plasma levels of 77 proteins measured using multiplex immune assays.Setting 
                  A tertiary referral dementia research center.Participants 
                  Thirty-three persons from families harboring PSEN1 or APP mutations, aged 19 to 59 years.Main Outcome Measures 
                  Protein levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs) and among APOE genotype groups, using multiple linear regression models.Results 
                  Twenty-one participants were FAD MCs and 12 were NCs. Six had the APOE ϵ2/3, 6 had the ϵ3/4, and 21 had the ϵ3/3 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 ϵ2 carriers, lowest in ϵ4 carriers, and intermediate in the ϵ3 carriers. Levels of multiple interleukins showed the opposite pattern and, among the ϵ4 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.Conclusions 
                  We found different patterns of inflammatory markers in young and middle-aged persons among APOE genotype groups. The APOE ϵ4 carriers had the lowest levels of apolipoprotein E. Young ϵ4 carriers have increased inflammatory markers that diminish with age. We demonstrated altered inflammatory responses in young and middle adulthood in ϵ4 carriers that may relate to AD risk later in life.