A Cannabis Molecule Reduces Plaque, Improves Cognition in Alzheimer’s

A two-week course of high doses of CBD helps restore the function of two proteins key to reducing the accumulation of beta-amyloid plaque, a hallmark of Alzheimer’s disease, and improves cognition in an experimental model of early onset familial Alzheimer’s, investigators report. The proteins TREM2 and IL-33 are important to the ability of the brain’s immune cells to literally consume dead cells and other debris like the beta-amyloid plaque that piles up in patients’ brains, and levels of both are decreased in Alzheimer’s.

The investigators report for the first time that CBD normalizes levels and function, improving cognition as it also reduces levels of the immune protein IL-6, which is associated with the high inflammation levels found in Alzheimer’s, says Dr. Babak Baban, immunologist and associate dean for research in the Dental College of Georgia (DCG) and the study’s corresponding author. There is a dire need for novel therapies to improve outcomes for patients with this condition, which is considered one of the fastest-growing health threats in the United States, DCG and Medical College of Georgia (MCG) investigators write in the Journal of Alzheimer’s Disease.

Right now we have two classes of drugs to treat Alzheimer’s,” says Dr. John Morgan, neurologist and director of the Movement and Memory Disorder Programs in the MCG Department of Neurology. “One class increases levels of the neurotransmitter acetylcholine, which also are decreased in Alzheimer’s, and another works through the NMDA receptors involved in communication between neurons and important to memory. But we have nothing that gets to the pathophysiology of the disease,” says Morgan, a study coauthor.

The DCG and MCG investigators decided to look at CBD’s ability to address some of the key brain systems that go awry in Alzheimer’s.

They found CBD appears to normalize levels of IL-33, a protein whose highest expression in humans is normally in the brain, where it helps sound the alarm that there is an invader like the beta-amyloid accumulation. There is emerging evidence of its role as a regulatory protein as well, whose function of either turning up or down the immune response depends on the environment, Baban says. In Alzheimer’s, that includes turning down inflammation and trying to restore balance to the immune system, he says.

CBD also improved expression of triggering receptor expressed on myeloid cells 2, or TREM2, which is found on the cell surface where it combines with another protein to transmit signals that activate cells, including immune cells. In the brain, its expression is on the microglial cells, a special population of immune cells found only in the brain where they are key to eliminating invaders like a virus and irrevocably damaged neurons.

Source: https://jagwire.augusta.edu/

How To Prevent The Formation Of Alzheimer’s Plaques

People who are affected by Alzheimer’s disease have a specific type of plaque, made of self-assembled molecules called β-amyloid (Aβ) peptides, that build up in the brain over time. This buildup is thought to contribute to loss of neural connectivity and cell death. Researchers are studying ways to prevent the peptides from forming these dangerous plaques in order to halt development of Alzheimer’s disease in the brain.

In a multidisciplinary study, scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory, along with collaborators from the Korean Institute of Science and Technology (KIST) and the Korea Advanced Institute of Science and Technology (KAIST), have developed an approach to prevent plaque formation by engineering a nano-sized device that captures the dangerous peptides before they can self-assemble.


Transmission Electron Microscopy (TEM) images of Aβ peptide samples in the presence of the Aβ nanodevices (scale bar: 200 nm). The lack of grains in the image indicates the effectiveness of the nanodevice in trapping the peptides

We’ve taken building blocks from nanotechnology and biology to engineer a high-capacity cage’ that traps the peptides and clears them from the brain.” — Elena Rozhkova, scientist, Center for Nanoscale Materials

The β-amyloid peptides arise from the breakdown of an amyloid precursor protein, a normal component of brain cells,” said Rosemarie Wilton, a molecular biologist in Argonne’s Biosciences division.In a healthy brain, these discarded peptides are eliminated.”

In brains prone to the development of Alzheimer’s, however, the brain does not eliminate the peptides, leaving them to conglomerate into the destructive plaques.

The idea is that, eventually, a slurry of our nanodevices could collect the peptides as they fall away from the cells — before they get a chance to aggregate,” added Elena Rozhkova, a scientist at Argonne’s Center for Nanoscale Materials (CNM), a DOE Office of Science User Facility.

Source: https://www.anl.gov/

Nanotherapy Reduces Plaque Buildup

A drug-coated nanoparticle reduces plaque buildup in mouse arteries without causing harmful side effects, researchers have found.

Atherosclerosis, the accumulation of plaque inside artery walls, can lead to heart attacks and strokes. It’s the world’s No. 1 killer. Available therapies treat risk factors such as high blood pressure and high cholesterol but fail to address the accumulation of diseased cells and inflammation within artery walls.

This is precision medicine,” said Nicholas Leeper, MD, professor of vascular surgery and cardiovascular medicine. “We used the nanotubes to deliver a payload like a Trojan horse.”

Leeper, who sees patients at Stanford Health Care’s vascular and endovascular care clinic, is a senior author of a paper about the research that was published Jan. 27 in Nature Nanotechnology. The other senior author is Bryan Smith, PhD, a former visiting associate professor at the School of Medicine. He is now an associate professor of biomedical engineering at Michigan State University.

Source: http://med.stanford.edu/

How To Detect Blocked Arteries Effectively

Heart disease and stroke are the world’s two most deadly diseases, causing over 15 million deaths in 2016 according to the World Health Organization. A key underlying factor in both of these global health crises is the common condition, atherosclerosis, or the build-up of fatty deposits, inflammation and plaque on the walls of blood vessels. By the age of 40, around half of us will have this condition, many without symptoms.

A new nanoparticle innovation from researchers in USC Viterbi’s Department of Biomedical Engineering may allow doctors to pinpoint when plaque becomes dangerous by detecting unstable calcifications that can trigger heart attacks and strokes. The research ­­— from Ph.D. student Deborah Chin under the supervision of Eun Ji Chung, the Dr. Karl Jacob Jr. and Karl Jacob III Early-Career Chair, in collaboration with Gregory Magee, assistant professor of clinical surgery from Keck School of Medicine of USC — was recently published in the Royal Society of Chemistry’s Journal of Materials Chemistry B on 25 September 2019.

When atherosclerosis occurs in coronary arteries, blockages due to plaque or calcification-induced ruptures can lead to a clot, cutting blood flow to the heart, which is the cause of most heart attacks. When the condition occurs in the vessels leading to the brain, it can cause a stroke.

A MICROSCOPIC VIEW OF ATHEROSCLEROSIS IN A PULMONARY ARTERY

An artery doesn’t need to be 80 percent blocked to be dangerous. An artery with 45% blockage by plaques could be more rupture-prone,” Chung said. “Just because it’s a big plaque doesn’t necessarily mean it’s an unstable plaque.

Chung said that when small calcium deposits, called microcalcifications, form within arterial plaques, the plaque can become rupture prone. However, identifying whether blood vessel calcification is unstable and likely to rupture is particularly difficult using traditional CT and MRI scanning methods, or angiography, which has other risks.

Angiography requires the use of catheters that are invasive and have inherent risks of tissue damage,” said Chin, the lead author. “CT scans on the other hand, involve ionizing radiation which can cause other detrimental effects to tissue.”

Source: https://viterbischool.usc.edu/

Nanoparticles Destroy Dental Plaque, Prevent Tooth Decay

Combine a diet high in sugar with poor oral hygiene habits and dental cavities, or caries, will likely result. The sugar triggers the formation of an acidic biofilm, known as plaque, on the teeth, eroding the surface. Early childhood caries is a severe form of tooth decay that affects one in every four children in the United States and hundreds of millions more globally. It’s a particularly severe problem in underprivileged populations.

Treatment with a nanoparticle and hydrogen peroxide (right panel) left little in the way of bacteria (in blue) or the sticky biofilm matrix (in red), making the combination a potent force against dental plaque

In a study published in Nature Communications, researchers led by Hyun (Michel) Koo of the University of Pennsylvania School of Dental Medicine in collaboration with David Cormode of Penn’s Perelman School of Medicine and School of Engineering and Applied Science used FDA-approved nanoparticles to effectively disrupt biofilms and prevent tooth decay in both an experimental human-plaque-like biofilm and in an animal model that mimics early-childhood caries. The nanoparticles break apart dental plaque through a unique pH-activated antibiofilm mechanism.

It displays an intriguing enzyme-like property whereby the catalytic activity is dramatically enhanced at acidic pH but is ‘switched off’ at neutral pH conditions,” says Koo, professor in Penn Dental Medicine’s Department of Orthodontics. “The nanoparticles act as a peroxidase, activating hydrogen peroxide, a commonly used antiseptic, to generate free radicals that potently dismantle and kill biofilms in pathological acidic conditions but not at physiological pH, thus providing a targeted effect.”

Because the caries-causing plaque is highly acidic, the new therapy is able to precisely target areas of the teeth harboring pathogenic biofilms without harming the surrounding oral tissues or microbiota. The particular iron-containing nanoparticle used in the experiments, ferumoxytol, is already FDA-approved to treat iron-deficiency, a promising indication that a topical application of the same nanoparticle, used at several-hundred-fold lower concentration, would also be safe for human use.

Source: https://penntoday.upenn.edu/