Plasma Ab42/40 levels differ by postmenopausal stage

Abstract

AbstractBackgroundAlthough all women who live into late life experience reproductive aging (menopause), there is little understanding about how reproductive aging, as distinct from chronologic aging, influences the development of AD. Studies indicate that some AD biomarkers differ between peri‐ and postmenopausal women, but no studies to date have examined AD biomarkers across (sub)stages of the postmenopause. Here we compared plasma Ab42/40 levels in Early versus Late Postmenopausal women. We hypothesized that plasma levels of Ab42/40 would be lower in the Late versus Early Postmenopause group.MethodParticipants included women from the Human Connectome Aging Project who had plasma Ab42/40 and were either in the Early Postmenopause (i.e., Stages +1a, +1b or +1c; >0 and <6 years after the final menstrual period; FMP) or Late Postmenopause (Stage +2; > 6 years after the FMP) according to the Stages of Reproductive Aging Workshop +10 criteria. Plasma Aβ42/40 was measured using an immunoprecipitation and liquid chromatography‐mass spectrometry assay. A univariate analysis of variance was conducted to compare plasma Ab42/40 in Early versus Late Postmenopause groups controlling for age, education, MOCA score, and ApoE carrier status.ResultThe sample included 42 women (mean age=66.2 years; mean MoCA=25.88; 73.8% white). Plasma Ab42/40 were significantly higher in the Early (n=10; mean age=55.77) versus Late Postmenopause (n=32; mean age=69.44) groups with mean values of 0.11 (SE=.002) and 0.103 (SE=.001), respectively, F(1,28)=7.23, p=.01. We restricted a second analysis to women age 60 years and under to optimally control for age differences between the groups (n=18, mean age=56.56 years; mean MOCA=26.04; mean education=17.17 years; 56% white, Early n=10). Again, plasma Ab42/40 were significantly higher in the Early (n=10; mean age=55.77) versus Late Postmenopause (n=32; mean age=57.56) groups with mean values of 0.11 (SE=.002) and 0.105 (SE=.003), respectively, F(1,13)=6.52, p =.025.ConclusionAdvanced reproductive stage, independent of chronologic age, may be associated with a lower plasma Ab42/40, a pattern shown to be predictive of the development of AD. These findings add to a body of AD biomarker studies showing differences between perimenopausal and postmenopausal women, and suggest that AD biomarkers also differ within distinct stages of the postmenopause.