Cerebrospinal beta-amyloid peptides(1-40) and (1-42) in severe preeclampsia and HELLP syndrome – a pilot study

Abstract

During pregnancy, substantial alterations in cerebral plasticity, vascular remodeling and neuronal growth occur in the maternal brain. We investigated whether concentrations of selected neurodiagnostic biomarkers in the cerebrospinal fluid of women with preeclampsia/HELLP syndrome differ from those in healthy controls using enzyme-linked immunosorbent assay technique. We found that tau protein concentrations (p = 0.016) and phospho-tau/tau ratio (p < 0.001) in cerebrospinal fluid were significantly lower in 39 preeclamptic women compared to 44 healthy controls during third trimester of pregnancy. Beta-amyloid(1-40)/(1-42) ratio was significantly higher in HELLP syndrome than in severe preeclampsia (8.49 + 2.73 vs. 4.71 + 1.65; p = 0.007). We conclude that betaamyloid(1-40)/(1-42) ratio in cerebrospinal fluid can discriminate severe preeclampsia and HELLP syndrome. High beta-amyloid peptide and low tau protein concentrations are associated with impaired development of the materno-feto-placental unit and correlate with placental dysfunction. During pregnancy, the invasion of trophoblast cells into maternal tissue of the uterus and the conversion of spiral arteries into wide sinusoids with low resistance and high flow are paramount for normal placental development 1. In preeclampsia (PE) placental development is impaired by defective deep placentation, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and imbalanced angiogenesis 2. Altered expression of proteins comes along with excess of antiangiogenic substances such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) and decreased levels of proangiogenic substances like placental growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) 3. Ciampa et al. observed in 13 patients with PE altered concentrations of proteins related to signaling pathways important for vascular remodeling, inflammation, and neuronal growth 4. Recent studies have shown that PE shares pathophysiologic features with recognized misfolding disorders and aggregation of proteins 4-8. There are several dysregulated proteins in PE but it is not clear whether aggregated proteins induce defective trophoblast invasion 4. D'Souza et al. reported that neurotrophic factors influence the development of the materno-feto-placental unit during pregnancy 9. Altered blood-brain barrier and impaired cerebral autoregulation may affect erebral blood flow in the maternal brain 10. Aggregated beta-amyloid peptides were observed in PE as well as in Alzheimer's disease 7. The presence of beta-amyloid aggregates in placentas of women with PE and intrauterine growth restriction (IUGR) further supports the notion that this condition goes with protein conformational disorders 6,11. Moreover, it was observed that short peptides occupying the self-recognition sites of beta-amyloid inhibit beta-amyloid aggregation 8. The aim of this study was to determine whether CSF concentrations of beta-amyloid peptides and tau protein differ between women with PE...

Signs of neuroaxonal injury in preeclampsia—A case control study

“…It is, however, possible that other mechanisms, potentially related to CSF dynamics, might play a role as well, but then all markers would move in the same direction, which was not the case in our study. In any case, our findings are in line with other publications reporting decreased CSF concentrations of tau in preeclampsia and in placental insufficiency [ 33 , 34 ]. These findings need to be confirmed in future studies.…”

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

“…Aside from its well-established role in neuronal cells, MAP-Tau contributes to the pathophysiology of placenta; it is upregulated in normal pregnancies and lowered in pre-eclampsia ( Bergman et al., 2018 ; Lederer et al., 2020 ). As viruses disrupt host immunity by converting MAP-Tau to pTau, placental function is likely altered.…”

Beta-amyloid peptides(1–42) and (1–40) in the cerebrospinal fluid during pregnancy: a prospective observational study

“…The question then arises whether a pathologic production or clearance defect of beta-amyloid peptides during pregnancy could be responsible for pregnancy-related central nervous system pathologies such as eclampsia, a severe complication of preeclampsia in which pregnant women suffer seizures (Duley 2009 ). In our previous work, beta-amyloid peptide levels in CSF were found to be lower in severe preeclampsia (Lederer et al 2020 ). In a postmortem study, a lower beta-amyloid load in CSF of patients with Alzheimer’s disease correlated with increased beta-amyloid aggregates in brain parenchyma (Blennow and Zetterberg 2018 ).…”

“…Beta-amyloid peptides are products of normal cell metabolism (Canobbio et al 2015 ) and have trophic properties: for example, they capture redox metal ions and thus dampen oxidative stress (Atwood et al 2003 ). In a recent study (Lederer et al 2020 ), we reported that beta-amyloid peptides correlate with placental dysfunction.…”