Methylated ccfDNA from plasma biomarkers of Alzheimer's disease using targeted bisulfite sequencing.

Aim: Noninvasive biomarkers such as methylated ccfDNA from plasma could help to support the diagnosis of Alzheimer's disease (AD). Methods: A targeted sequencing protocol was developed to identify candidate biomarkers of AD in methylated ccfDNA extracted from plasma. Results: The authors identified differentially methylated CpGs, regions of which were the same as those identified in previous AD studies. Specifically, a differentially methylated CpG of the LHX2 gene previously identified in a plasma study of AD was replicated in the study. The MBP and DUSP22 regions have been identified in other brain studies of AD and in the authors' study. Conclusion: Although these biomarkers must be validated in other cohorts, methylated ccfDNA could be a relevant noninvasive biomarker in AD.

Currently, the diagnosis of Alzheimer's disease (AD) is based on symptoms and medical imaging, and definitive clinical diagnosis is only possible postmortem. The identification of noninvasive biomarkers such as methylated ccfDNA is crucial for the diagnosis, prognosis and monitoring of AD. However, the analysis of ccfDNA from plasma is a challenge because it is highly fragmented and present in low amounts and originates from various tissues. The authors developed a targeted sequencing protocol using genes previously reported in AD literature (brain, blood and plasma) to identify potential noninvasive biomarkers in plasma. The authors identified positions identical to those in the literature as well as potential novel sites located in the promoter, exon and intron regions of these genes. Although these results must be validated in a large cohort, methylated ccfDNA could be a useful noninvasive biomarker for AD.

Repeated potassium iodide exposure during pregnancy impairs progeny's brain development.

Protracted radioiodine release may require repeated intake of potassium iodide (KI) to protect thyroid gland. It is well established that iodine excess inhibits transiently the thyroid function. As developing fetus depends on maternal thyroid hormones (TH) supply, more knowledge is needed about the plausible effects that repeated KI intake can cause in this sensitive population, especially that even subtle variation of maternal thyroid function may have persistent consequences on progeny brain processing. The aim of this study is to assess the consequences of repeated intake of KI during pregnancy on the progeny's thyroid function and brain development. To do so pregnant Wistar rats received KI over eight days, and then thirty days after the weaning, male progeny was subjected to behavior test. Pituitary and thyroid hormones level, anti-thyroid antibodies level, organs morphology, gene expression and global DNA methylation were assessed. Thirty days after the weaning, KI-exposed male progeny showed an uncommon hormonal status, characterized by a decrease of both thyroid-stimulating hormone (-28%) and free thyroxine (-7%) levels. Motor coordination was altered in KI-exposed male progeny. At the cerebellar level, we observed a decrease of mRNA expression of DCX (-42%) and RC3 (-85%); on the other hand, at the cortical level, mRNA expression of MBP (+71%), MOBP (+90%) and Kcna1 (+42%) was increased. To conclude, repeated KI prophylaxis is not adequate during pregnancy since it led to long-term irreversible neurotoxicity in the male progeny.