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Background: Type I interferon signalling dysregulation is a hallmark of SARS‐CoV‐2 infection and among significantly perturbed pathways in Alzheimer's disease. In a previous study, we predicted the involvement of this pathway in the development of SARS‐CoV‐2 Associated Neurocognitive Disorder (SAND) via a crosstalk between peripheral immunity and the CNS. The purpose of this study is to determine whether current data support provide external validation to our pathogenetic hypothesis. Method: Data for our validation analyses were leveraged from studies of frontal cortex (FC) transcriptomes donated by Alzheimer's disease and COVID‐19 patients vs. controls, respectively. An additional dataset of nasal epithelial cells from COVID‐19 patients was also used as a putative crosstalk site. Enrichment analyses were employed to provide an unbiased estimate of the enrichment of Type I interferon responses. Furthermore, we performed a literature search in order to identify studies on the effects of COVID‐19 on two different settings: (a) to determine the effects of peripheral exosome cargo on CNS tissue (b) to determine the cargo of neuronal‐derived exosomes. For enrichment analyses, a false discover rate (FDR) <0.05 was considered statistically significant. Result: The type I interferon pathway (IFN‐I; GO:0060337) was significantly enriched in both Alzheimer's disease and COVID‐19 FC transcriptomes, as well as nasal epithelia of COVID‐19 patients. Common genes in both IFN‐I FC signatures included PSMB8, IP6K2, IFI35, EGR1, ISG20, MYD88, IFITM1, SP100, GBP2, IFITM3, OASL, IRF1, IRF2, MX2, IFNA2, IRF9, IFIT3, STAT2, HLA‐C, SAMHD1, IFI27, IFITM2, IRF7, BST2. At least one study reports on miR‐148a and miR‐590 as exosomal cargo of infected non‐neuronal cells capable of affecting IFN‐I responses and inducing microglial activation, supporting the role of exosomes as facilitators of IFN‐I crosstalk between the periphery and the CNS. Correspondingly, at least one study reports on proteopathic seeds as cargo of neuron‐derived exosomes. Conclusion: Independent studies and data support continue to corroborate our hypothesis that type I interferon pathway dysregulation as a result of peripheral – CNS immune crosstalk may mediate neuroinflammation and Alzheimer's disease‐like pathology as observed in SAND. [ABSTRACT FROM AUTHOR]

Purpose: Aberrant methylation, as an epigenetic phenomenon, may precede and regulate the expression of genes involved in transformation mechanisms that lead to leukemogenesis of hemopoietic cells. The genes involved mostly encode transcription factors and cell cycle specific inhibitors. The aim of this project was to study the DNA methylation pattern of c-myc, c-fos and p53 in myelodysplastic syndromes (MDS) and in acute non-lymphocytic leukemias (ANLL)., Patients and Methods: DNA was isolated from the monocyte cell layer harvested from bone marrow or peripheral blood samples of 44 patients suffering from MDS and ANLL. Genomic DNA was digested with methylation-specific enzymes, and was electrophoresed and hybridized with probes specific for human c-myc, c-fos and p53 genes., Results: In MDS, the c-myc gene in exons 2 and 3 was regionally hypomethylated, whereas exon 2 in ANLL was hypermethylated and exon 3 hypomethylated. The c-fos gene was hypomethylated in ANLL type 4 and presented aberrant hypomethylation in the different types of MDS. The p53 anti-oncogene appeared extensively hypomethylated in MDS., Conclusion: Aberrant DNA methylation pattern of the c-myc, c-fos and p53 tumor suppressor gene seems to be a primary event in the transformation process from myelodysplasia to acute leukemia, affecting their expression, and, consequently, altering the proliferation, differentiation or apoptosis of hemopoietic precursor cells. The p53 hypomethylation predisposes to critical mutations that enhance the transformation process of myelodysplasia to leukemia. The recognition of altered methylation of these genes in myelodysplasia may have prognostic implications and may lead to novel therapeutic modalities.