TREM2 variants as a possible cause of frontotemporal dementia with distinct neuroimaging features.

BACKGROUND AND PURPOSE: Nasu-Hakola disease (NHD) is a rare, autosomal recessive disorder characterized by skeletal and neurological symptoms. Behavioral symptoms with cognitive impairment may mimic the behavioral variant of frontotemporal dementia (bvFTD) and other early-onset dementias. Our patients were analyzed and the literature was reviewed to delineate neurological and neuroimaging findings suggestive of NHD. METHOD: Fourteen patients carrying a pathogenic mutation in the TREM2 gene were found in our database. Demographic, clinical, laboratory and radiological data were retrieved and analyzed. RESULTS: The presenting clinical picture was behavioral changes with cognitive decline resembling bvFTD in all patients. The mean age was 37.1 ± 4.97 years and the mean duration of the disease was 8.9 ± 3.51 years. Only two patients had typical bone cysts. Seven patients had bilateral calcification of the basal ganglia in computed tomography of the brain. Magnetic resonance imaging of the brain revealed severe atrophy of the corpus callosum, enlargement of the ventricles, atrophy of the caudate nuclei and periventricular white matter changes in all patients. Symmetrical global atrophy of the brain mainly affecting frontoparietal and lateral temporal regions were observed in all cases, and 13 patients had atrophy of the hippocampus. Cerebrospinal fluid examination of 10 patients showed elevated protein levels in six and the presence of oligoclonal bands in four patients. CONCLUSION: A combination of white matter changes, enlarged ventricles, atrophy of the caudate nuclei and thinning of the corpus callosum in magnetic resonance imaging strongly suggests NHD in patients with FTD syndrome. Molecular genetic analysis should be performed in suspected cases, and families should receive genetic counseling.

A genetic link between risk for Alzheimer's disease and severe COVID-19 outcomes via the OAS1 gene.

Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer's disease, by its enrichment in transcriptional networks expressed by microglia. However, the function of OAS1 within microglia was not known. Using genotyping from 1313 individuals with sporadic Alzheimer's disease and 1234 control individuals, we confirm the OAS1 variant, rs1131454, is associated with increased risk for Alzheimer's disease. The same OAS1 locus has been recently associated with severe coronavirus disease 2019 (COVID-19) outcomes, linking risk for both diseases. The single nucleotide polymorphisms rs1131454(A) and rs4766676(T) are associated with Alzheimer's disease, and rs10735079(A) and rs6489867(T) are associated with severe COVID-19, where the risk alleles are linked with decreased OAS1 expression. Analysing single-cell RNA-sequencing data of myeloid cells from Alzheimer's disease and COVID-19 patients, we identify co-expression networks containing interferon (IFN)-responsive genes, including OAS1, which are significantly upregulated with age and both diseases. In human induced pluripotent stem cell-derived microglia with lowered OAS1 expression, we show exaggerated production of TNF-α with IFN-γ stimulation, indicating OAS1 is required to limit the pro-inflammatory response of myeloid cells. Collectively, our data support a link between genetic risk for Alzheimer's disease and susceptibility to critical illness with COVID-19 centred on OAS1, a finding with potential implications for future treatments of Alzheimer's disease and COVID-19, and development of biomarkers to track disease progression.

Effectiveness of booster BCG vaccination in preventing Covid-19 infection.

The evidence that BCG (bacille Calmette-Guerin) vaccine may increase the ability of the immune system to fight off pathogens other than tuberculosis has been studied in the past. This nonspecific immunity gained our interest, especially after initial reports of less cases in countries with universal BCG vaccination. In hopes of possible protective immunity, all staff of the Emirates International Hospital (United Arab Emirates) were offered a booster BCG vaccine in early March 2020. All the hospital staff were then tested for Covid-19 infection by the end of June 2020. We divided the subjects into two groups: booster vaccinated versus unvaccinated. The rate of Covid-19 infection was compared between the groups. Criteria included all staff who were offered the vaccine. Seventy-one subjects received the booster vaccination. This group had zero cases of positive COVID 19 infection. Two hundred nine subjects did not receive the vaccination, with 18 positive PCR confirmed COVID 19 cases. The infection rate in the unvaccinated group was 8.6% versus zero in the booster vaccinated group (Fisher's exact test p-value = .004). Our findings demonstrated the potential effectiveness of the booster BCG vaccine, specifically the booster in preventing Covid-19 infections in an elevated-risk healthcare population.

An overview of the use of biomaterials, nanotechnology, and stem cells for detection and treatment of COVID-19: towards a framework to address future global pandemics.

A novel SARS-like coronavirus (severe acute respiratory syndrome-related coronavirus-2, SARS-CoV-2) outbreak has recently become a worldwide pandemic. Researchers from various disciplinary backgrounds (social to natural science, health and medicine, etc.) have studied different aspects of the pandemic. The current situation has revealed how the ongoing development of nanotechnology and nanomedicine can accelerate the fight against the novel viruses. A comprehensive solution to this and future pandemic outbreaks includes preventing the spread of the virus through anti-viral personal protective equipment (PPE) and anti-viral surfaces, plus efforts to encourage behavior to minimize risks. Studies of previously introduced anti-viral biomaterials and their optimization to fight against SARS-CoV-2 is the foundation of most of the recent progress. The identification of non-symptomatic patients and symptomatic patients is vital. Reviewing published research highlights the pivotal roles of nanotechnology and biomaterials in the development and efficiency of detection techniques, e.g., by applying nanotechnology and nanomedicine as part of the road map in the treatment of coronavirus disease 2019 (COVID-19) patients. In this review, we discuss efforts to deploy nanotechnology, biomaterials, and stem cells in each step of the fight against SARS-CoV-2, which may provide a framework for future efforts in combating global pandemics.