Preanalytical stability of plasma biomarkers for Alzheimer's disease pathology

INTRODUCTION: Plasma tests have demonstrated high diagnostic accuracy for identifying Alzheimer's disease pathology. To facilitate the transition to clinical utility, we assessed whether plasma storage duration and temperature affect the biomarker concentrations. METHODS: Plasma samples from 13 participants were stored at +4°C and +18°C. Concentrations of six biomarkers were measured after 2, 4, 6, 8, 10, and 24 h by single molecule array assays. RESULTS: Phosphorylated tau 181 (p-tau181), phosphorylated tau 231 (p-tau231), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) concentrations were unchanged both when stored at +4°C and +18°C. Amyloid-β 40 (Aβ40) and amyloid-β 42 (Aβ42) concentrations were stable for 24 h at +4°C but declined when stored at +18°C for longer than 6 h. This decline did not affect the Aβ42/Aβ40 ratio. DISCUSSION: Plasma samples can be stored for 24 h at +4°C or +18°C and result in valid assay results for p-tau181, p-tau231, Aβ42/Aβ40 ratio, GFAP, and NfL. HIGHLIGHTS: Plasma samples were stored for 24 h at +4°C and +18°C, mimicking clinical practice.Concentrations for Alzheimer's disease biomarkers were measured at six time-points.p-tau181, p-tau231, NfL, and GFAP concentrations were unchanged during the experiment.Storage at +18°C affected Aβ40 and Aβ42 concentrations while storage at +4°C did not. The Aβ42/Aβ40 ratio was unaffected.These plasma tests seem suitable for use in general practice

Hypertension in Pregnancy and Offspring Cardiovascular Risk in Young Adulthood:Prospective and Sibling Studies in the HUNT Study (Nord-Trøndelag Health Study) in Norway

Women with hypertensive disorders in pregnancy are at increased lifetime risk for cardiovascular disease. We examined the offspring’s cardiovascular risk profile in young adulthood and their siblings’ cardiovascular risk profile. From the HUNT study (Nord-Trøndelag Health Study) in Norway, 15 778 participants (mean age: 29 years), including 210 sibling groups, were linked to information from the Medical Birth Registry of Norway. Blood pressure, anthropometry, serum lipids, and C-reactive protein were assessed. Seven hundred and six participants were born after exposure to maternal hypertension in pregnancy: 336 mothers had gestational hypertension, 343 had term preeclampsia, and 27 had preterm preeclampsia. Offspring whose mothers had hypertension in pregnancy had 2.7 (95% confidence interval, 1.8–3.5) mm Hg higher systolic blood pressure, 1.5 (0.9–2.1) mm Hg higher diastolic blood pressure, 0.66 (0.31–1.01) kg/m2 higher body mass index, and 1.49 (0.65–2.33) cm wider waist circumference, compared with offspring of normotensive pregnancies. Similar differences were observed for gestational hypertension and term preeclampsia. Term preeclampsia was also associated with higher concentrations of non–high-density lipoprotein cholesterol (0.14 mmol/L, 0.03–0.25) and triglycerides (0.13 mmol/L, 0.06–0.21). Siblings born after a normotensive pregnancy had nearly identical risk factor levels as siblings born after maternal hypertension. Offspring born after maternal hypertension in pregnancy have a more adverse cardiovascular risk profile in young adulthood than offspring of normotensive pregnancies. Their siblings, born after a normotensive pregnancy, have a similar risk profile, suggesting that shared genes or lifestyle may account for the association, rather than an intrauterine effect. All children of mothers who have experienced hypertension in pregnancy may be at increased lifetime risk of cardiovascular disease

Maternal Preeclampsia and Androgens in the Offspring around Puberty: A Follow-Up Study

<div><p>Background</p><p>Children born after preeclampsia may have a dominant androgen profile in puberty compared with other children. Circulating androgen concentrations at 11–12 years of age were compared between offspring born after preeclampsia, and children whose mothers did not have preeclampsia.</p><p>Methods</p><p>A total of 611 mother-offspring pairs were followed up 11 (daughters) or 12 (sons) years after birth: 218 pairs in the preeclampsia group, and 383 pairs without preeclampsia. Circulating total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor I (IGF-I) were measured in the children. In boys, testicular volume was also measured.</p><p>Results</p><p>Among girls born after preeclampsia, DHEAS concentrations were higher than in unexposed girls (p<0.001), however, girls born after preeclampsia with severe features had the lowest DHEAS levels. In contrast, testosterone concentrations were highest in girls born after preeclampsia with severe features, both compared to other girls in the preeclampsia group, and compared to unexposed girls (p<0.001). For boys, testosterone concentrations were higher in the preeclampsia group compared with unexposed boys (p<0.001), and boys born after preeclampsia with severe features had the lowest concentrations of DHEAS. Compared with unexposed boys, testicular volume (p = 0.015) and IGF-I (p = 0.004) were higher for boys in the preeclampsia group, except for boys in the clinically severe preeclampsia group.</p><p>Conclusions</p><p><i>In utero</i> exposure to preeclampsia is associated with androgen hormonal patterns in early puberty that depend on clinical severity of preeclampsia and sex of the offspring. The hormonal differences may reflect different timing of pubertal development, and may have consequences for future health of the offspring.</p></div

Hormonal differences^a from the reference group (no preeclampsia) among offspring at 11–12 years by exposure to preeclampsia <i>in utero</i>^b.

<p>Hormonal differences<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0167714#t002fn001" target="_blank">^a</a> from the reference group (no preeclampsia) among offspring at 11–12 years by exposure to preeclampsia <i>in utero</i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0167714#t002fn002" target="_blank">^b</a>.</p

Maternal characteristics according to preeclampsia status at delivery.

<p>Maternal characteristics according to preeclampsia status at delivery.</p