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Archive - Apr 13, 2018

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Simple, Inexpensive Blood Test Detects Alzheimer’s Years Before Symptoms Occur

There is currently no cure for Alzheimer’s disease. It is often argued that progress in drug research has been hampered by the fact that the disease can only be diagnosed when it is too late for an effective intervention. Alzheimer’s disease is thought to begin long before patients show typical symptoms like memory loss. Scientists have now developed a blood test for Alzheimer’s disease and found that it can detect early indicators of the disease long before the first symptoms appear in patients. The blood test would thus offer an opportunity to identify those at risk and may thereby open the door to new avenues in drug discovery. The research was published online on April 6, 2018 in EMBO Molecular Medicine. The open-access article is titled “Amyloid Blood Biomarker Detects Alzheimer's Disease.” One of the hallmarks of Alzheimer's disease is the accumulation of amyloid-β plaques in the patient’s brain. The blood test, developed by Dr. Klaus Gerwert and his team at Ruhr University Bochum, Germany, works by measuring the relative amounts of a pathological and a healthy form of amyloid-β in the blood. The pathological form is a misfolded version of this molecule and known to initiate the formation of toxic plaques in the brain. Toxic amyloid-β molecules start accumulating in the patients’ body 15-20 years before disease onset. In the present study, Dr. Gerwert and colleagues from Germany and Sweden addressed whether the blood test would be able to pick up indications of pathological amyloid-β in very early phases of the disease. The researchers first focused on patients in the early, so-called “prodromal” stages of the disease from the Swedish BioFINDER cohort conducted by Dr. Oskar Hanson.

Germ Cells in the Teleost Fish Medaka Have an Inherent Feminizing Effect

The gender of living organisms is determined either by genetic factors and/or by environmental factors. Interestingly, however, a team of researchers led by Nagoya University scientists previously found that the occurrence of more germ cells - biological cells capable of uniting with one from the opposite sex to form a new individual - in female medaka (teleost fish) gonads is essential for female differentiation of gonads. When germ cells are removed in medaka, XX (female) fish show female-to-male sex reversal, while XY (male) fish with excessive germ cells, which is usually associated with egg production, exhibit male-to-female sex reversal. "This finding implies that, in addition to the most well- known role of germ cells developing into eggs or sperm and produce the next generation, germ cells have a unique and surprising potential to change their surrounding environment," says Dr. Toshiya Nishimura, first author of the current study. "However, the molecular basis of, and the stage of gametogenesis critical for, feminization remain unknown." This question set the researchers to delve more deeply into the topic. In their latest study, they generated three different medaka mutants to demonstrate that the feminizing effect of germ cells is not a result of the progression of gametogenesis or a sexual fate decision of germ cells. They found that the different stages of germ cells in XX mutants have an ability to feminize the gonads, resulting in the formation of gonads with ovarian structures. In addition to normal ovarian development, the increased number of gonocytes (fetal and neonatal germ cells) is sufficient for male-to-female sex reversal in XY medaka.

Somatic Genomic Editing Will Enable Precision Tumor Modeling and “Greatly Accelerate the Pre-Clinical Testing of Novel Targeted Therapies” for Cancer

Researchers from the Seve Ballesteros Foundation-CNIO Brain Tumor Group at the Spanish National Cancer Research Centre (CNIO) have developed an extremely powerful and versatile mouse model that will improve cancer research and accelerate pre-clinical testing of novel targeted therapies. Their work was published online on April 13, 2018 in Nature Communications. The open-access article is titled “Somatic Genome Editing with the RCAS-TVA-CRISPR-Cas9 System For Precision Tumor Modeling.” “A current high priority in cancer research is to functionally validate candidate genetic alterations that are relevant for cancer progression and treatment response. In order to do so, it is essential to develop flexible models that can speed up the identification of cancer driver genes among the large number of passenger alterations,” state the authors. In order to achieve this, researchers led by Dr. Massimo Squatrito combined two technologies - the genome editing tool CRISPR-Cas9 and the gene delivery system RCAS/TVA - to generate a mouse model that brings the possibility of mimicking the genetic complexity of cancer. Dr. Barbara Oldrini and Dr. Álvaro Curiel-García, co-lead authors in the study, used this novel model to recapitulate some of the genetic alterations found in gliomas. In particular, they studied a gene fusion encoding a family of kinases called NTRK and a common mutation of the BRAF gene, both identified not only in glioma, but also in other tumor types. "What we have shown using this new model is that we now have the ability to generate specific complex genetic alterations and to study how they contribute to glioma pathogenesis,” explains Dr. Squatrito.