Research Roundup: ADHD Drug Appears to Delay Alzheimer’s Symptoms and More

Brain

Alzheimer’s disease is associated with two abnormal proteins found in patients’ brains: beta-amyloid and tau. Biogen’s Aduhelm (aducanumab) was approved by the U.S. Food and Drug Administration (FDA) for its ability to clear beta-amyloid. Researchers at Emory investigated the use of an FDA-approved ADHD medication on patients with mild Alzheimer’s symptoms and found it appeared to reduce levels of tau. For that and more research stories, continue reading.

ADHD Drug Appears to Delay Alzheimer’s Symptoms

Researchers at Emory Health Sciences conducted a Phase II clinical study using a drug for attention-deficit/hyperactivity disorder (ADHD) in people with early symptoms of Alzheimer’s disease. They evaluated 39 people with mild cognitive impairment (MCK) and treated them with an approved ADHD drug, atomoxetine (Strattera), for six months. They found the drug decreased levels of tau proteins, a form of abnormal protein found in the brains of Alzheimer’s patients, in cerebrospinal fluid (CSF), and other markers of neuro-inflammation were normalized. Two abnormal proteins are associated with Alzheimer’s beta-amyloid and tau. The research was published in the journal Brain.

“We are encouraged by the results of the trial,” said Dr. Allan Levey, lead author and Professor of Neurology at Emory University School of Medicine and director of the Goizueta Institute @Emory Brain Health. “The treatment was safe, well tolerated in individuals with mild cognitive impairment, and modulated the brain neurotransmitter norepinephrine just as we hypothesized. Moreover, our exploratory studies show promising results on imaging and spinal fluid biomarkers which need to be followed up in larger studies with longer period of treatment.”

The goal of the research, and why they chose atomoxetine, was to boost norepinephrine levels in the brain. The research team theorized this could stabilize a vulnerable region of the brain against Alzheimer’s-associated neurodegeneration. Norepinephrine is manufactured primarily by the locus coeruleus, a part of the brainstem that is often the first to show Alzheimer’s-related pathology, even in healthy, middle-aged people. It is believed that norepinephrine reduces inflammation and stimulate microglia, which clear debris from the brain. The actual reduction of tau was relatively low, about 5%, but they theorize that longer duration of treatment could provide greater tau reduction.

Hobbies and Exercise Can Reduce Risk of Dementia

Research out of Simon Fraser University confirms what many other studies have suggested: exercise, hobbies and social engagement can reduce the risk of memory decline as we age. The research found that a combination of hobbies such as exercise and connecting with loved ones can decrease memory decline in people between the ages of 65 and 89 more than any single activity. The research used data from the National Institute on Aging’s Health and Retirement Study that included 3,210 participants in the age group. They were questioned how often they engaged in 33 activities. Then they utilized machine learning to analyze the impact on memory of the various activities, which ranged from baking or cooking, reading, playing games or cards, to walking for 20 minutes. Genetics are probably the main factor influencing cognitive health, but the activities you participate in have an effect as well.

HIV Drugs May Show Promise for Low-Grade Brain Tumors

Researchers at University of Plymouth found that drugs used to treat HIV might be effective in treating the most common type of primary brain tumor, such as meningioma and acoustic neuroma brain tumors. The research team previously demonstrated that a tumor suppressor, Merlin, contributes to the development of meningioma, acoustic neuroma and ependymoma tumors. It also is involved in neurofibromatosis type 2. In the latest study, they evaluated the role a specific section of DNA plays in tumor development, specifically endogenous retrovirus HERV-K. They found high levels of HERV-K proteins in meningioma and schwannoma cells, and further, several antiviral drugs, specifically retroviral protease inhibitors ritonavir, atazanavir, and lopinavir, already approved for HIV/AIDS, targeted the proteins.

Possible New Target to Treat TB

Investigators at Weill Cornell Medicine have identified a potential new target for the treatment of tuberculosis (TB). They were investigating the role of an enzyme that is vital for the Mycobacterium tuberculosis (Mtb) bacteria to break down available fatty acids that they use for energy. By deleting the enzyme, EtfDMtb, they prevented Mtb from infecting mice. By silencing that enzyme, they starved the Mtb and also killed it. Mtb typically has multiple fatty acid metabolic pathways, but they identified a three-component complex that is crucial for Mtb’s normal growth and survival. Two enzymes, EtfAMtb and EtfMtb form an enzyme that works with yet another enzyme, EtfDMtb, which is a promising drug target.

Third Shot of Moderna COVID-19 Vaccine Neutralizes Omicron

Moderna announced preliminary data suggesting the third booster shot of its mRNA vaccine offers protection against the Omicron variant of COVID-19. In laboratory studies of blood plasma from people who received the two-shot regimen and a three-shot regimen, the three-shot produced a 37-fold increase in neutralizing antibody levels against Omicron compared to the two-shot. The third shot is half a dose of the two original shots. They also tested a full 100 microgram dose of the third shot and it increased antibody levels about 83-fold compared to pre-boost levels.

Astrocytes Associated with Memory Flexibility

Scientists with the Institute for Basic Science in Daejeon, South Korea noted that astrocytes, star-shaped cells in the brain, regulate cognitive flexibility. The cells simultaneously regulate and integrate synaptic plasticity of local synapses, which is important for helping cognitive flexibility. Research into diseases such as autism, schizophrenia, and early Alzheimer’s have shown that reduced function of N-methyl-D-aspartate receptors (NMDARs) are associated with development of these diseases. NMDARs are vital receptors for synaptic plasticity and are activated by several agonists and co-agonists, including D-serine. By using astrocyte-specific gene regulation, the investigators demonstrated that astrocytes synthesize D-serine and release it via Best1, a calcium-activated channel. Astrocytes were already known to release glutamate through Best1, so the co-release of D-serine and glutamate suggests that astrocytes are prime regulators of NMDAR activity and synaptic plasticity.

“Since each astrocyte is in contact with over 100,000 synapses, astrocytes can control numerous synapses and integrate synaptic plasticity simultaneously,” said KOH Wuhyun, the first author of the study.

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