Research Roundup: New Protein Linked to Alzheimer’s Identified and More

Alzheimer's Research

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.

New Protein IDed that May Cause Alzheimer’s

Scientists at the University of Tokyo tested 19,151 individual genes looking for their effect on amyloid beta levels. Amyloid beta is one of the proteins that accumulates in the brains of Alzheimer’s patients and is generally viewed as one of the primary drivers of the disease. They identified a new protein using CRISPR/Cas9 gene editing, called calcium and integrin-binding protein 1 (CIB1). They found that cells without functional CIB1 genes generate abnormally high levels of amyloid beta protein. The research was published in FASEB Journal.

“We believe this is the first time anyone has used this CRISPR/Cas9 genetic screening technique to look for changes in amyloid beta production,” said Yukiko Hori, co-first author and lecturer at the University of Tokyo.

In normal, healthy cells, CIB1 is not directly involved with processing amyloid beta, but it stays attached to another protein, gamma secretase inside cells and at the cell membrane. In cells that don’t have CIB1, gamma secretase stays inside the cell longer and doesn’t leave the membrane. Amyloid beta undergoes multiple steps before reaching its final form. Normally, gamma secretase processes amyloid beta precursors to help produce the final amyloid beta protein. This happens inside the cell, then gamma secretase moves to the cells outer surface membrane.

Patients diagnosed with early-stage Alzheimer’s disease have lower levels of CIB1 in their brains, while people with late-stage Alzheimer’s have higher-than-healthy levels of CIB1.

“We cannot say for certain why CIB1 is increased in late-stage Alzheimer’s disease,” said Taisuke Tomita, who runs the research lab where the study was conducted. “What is important is that in both the early and late stages of Alzheimer’s disease, something is abnormal about the regulation of CIB1.”

Possible Approach to Improving Gene Therapy

Investigators at the University of Groningen have developed a technique that may improve gene therapies. They use DNA/lipid complexes (lipoplexes). Because the viruses used traditionally in gene therapies can cause an immune response and the cells’ endosomes tend to degrade DNA or other particles, the lipoplex provides protection. They can fuse with the endosome membrane, which prevents degradation.

Gene Promoters that Can Be Used to Treat Neurological Diseases

Researchers at Princeton Neuroscience Institute have developed new gene promoters that act like switches to turn on gene expression. They can be used in gene therapy, with a particular interest in neurological diseases such as Parkinson’s and Alzheimer’s. Viruses are used to carry genes into cells during gene therapy, typically adeno-associated viruses. The Princeton team used promoters found in herpes viruses, which take up less space than existing promoters and allow the transport of larger genes or multiple genes. They are also long-lasting.

Biosensor to Detect SARS-CoV-2 in the Air

Researchers at Switzerland-based Empa, ETH Zurich and Zurich University Hospital have developed a sensor that has the potential to identify SARS-CoV-2, the novel coronavirus that causes COVID-19, in the air. The work is led by Jing Wang at Empa, who usually works on measuring and analyzing airborne pollutants. The sensor has reliably shown it can identify the first SARS-CoV virus that was responsible for the SARS pandemic in 2003. It has numerous similarities to SARS-CoV-2. “Tests showed that the sensor can clearly distinguish between the very similar RNA sequences of the two viruses,” Jing Wang said. And the results appear in minutes.

Possible Gene Therapy for Glaucoma

Glaucoma is a common condition of the eye involved fluid buildup in the front part of the eye. It affects more than 64 million people globally and is the leading cause of irreversible blindness. Current treatments include eye drops, laser or surgery. Researchers at the University of Bristol demonstrated that a single injection of a gene therapy using CRISPR and a gene called Aquaporin 1 targeting the ciliary body, where fluid is produced within the eye, led to reduced eye pressure.

More Evidence Parkinson’s is an Autoimmune Disease

A study co-led by investigators at the La Jolla Institute for Allergy and Immunology (LJI) adds to the theory that Parkinson’s disease is at least partly an autoimmune disease. The research was published in Nature Communications. Science has known for some time that the clumps of a damaged protein known as alpha-synuclein build up in the dopamine-producing brain cells of Parkinson’s disease patients. The clumps lead to death of the cells and cause motor symptoms and cognitive decline.

“Once these cells are gone, they’re gone,” said Cecilia Lindestam Arlehamn, first author of the study and LJI research assistant professor. “So if you are able to diagnose the disease as early as possible, it could make a huge difference.”

A 2017 study showed that alpha-synuclein attracted certain type of T-cells, causing them to mistakenly attack brain cells, which potentially contributed to the progression of Parkinson’s. The new findings found that the T-cells that react to alpha-synuclein are the most abundant when patients are first diagnosed with the disease. They tend to disappear later in the disease and by 10 years after diagnosis, few patients still have them.

“This tells us that detection of T-cell responses could help in the diagnosis of people at risk or in early stages of disease development, when many of the symptoms have not been detected yet,” said LJI professor Alessandro Sette, who co-led the research with David Sulzer of the Columbia University Medical Center. “Importantly, we could dream of a scenario where early interference with T-cell responses could prevent the disease from manifesting itself or progressing.”

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