NeuroInflammation Critical in the Developement of Alzheimer’s

Doctors regard amyloid plaque lodged between the brain’s nerve cells and tangled tau protein fibers forming within the cells as the hallmark of Alzheimer’s disease. However, amyloid plaque — consisting of broken pieces of protein that clump together — is also present in the brains of older adults who do not develop Alzheimer’s, suggesting another factor is triggering the disease.

A new study finds that inflammation in the brain drives the progression from the presence of amyloid plaque and tau tangles to the onset of dementia and Alzheimer’s disease.
Lead author of the study, Dr. Tharick Pascoal, Ph.D., assistant professor of psychiatry and neurology at the University of Pittsburgh School of Medicine, PA, explains:

Many [older adults] have amyloid plaques in their brains but never progress to developing Alzheimer’s disease. We know that amyloid accumulation on its own is not enough to cause dementia — our results suggest that it is the interaction between neuroinflammation and amyloid pathology that unleashes tau propagation and eventually leads to widespread brain damage and cognitive impairment.”

While scientists have observed neuroinflammation in people with Alzheimer’s before, the new study reveals for the first time its critical role in the development of the disease. The research finds that activating the brain’s immune cells — its microglial cellspromotes the spread of tangled tau proteins that comprise amyloid plaque.

Heather M. Snyder, Ph.D., Alzheimer’s Association vice president of medical and scientific relations, who was not involved in the study, explained the purpose of neuroinflammation to Medical News Today. The Alzheimer’s Association contributed funding to the research.

Inflammation has an important role in fighting off infection and other pathogens in the body, including in the brain and central nervous system,” said Snyder. Microglia “help clear debris (damaged neurons, infections) from the brain.” “However,” adds Dr. Snyder, “a sustained inflammatory response, or a change from acute to chronic neuroinflammation, may contribute to the underlying biology of several neurodegenerative disorders.

Inflammation is not by itself associated with cognitive impairment, daid Dr. Pascoal. “However when neuroinflammation converges with amyloid pathology, the interaction potentiates tau pathology. As a consequence, the coexistence of these three processes in the brain — amyloid, neuroinflammation, and tau pathology — determines cognitive deterioration.”

Results suggest that the combination of anti-amyloid with anti-inflammatory therapies in the early stages of the disease, when the pathology of tau is still confined to the temporal cortex, would maximize the efficacy of these drugs.”

The study appears in Nature Medicine.

Source: https://www.medicalnewstoday.com/

Inhaled Nanobodies Effective Against COVID-19

In a paper published today in Science Advances, researchers from the University of Pittsburgh School of Medicine showed that inhalable nanobodies targeting the spike protein of the SARS-CoV-2 coronavirus can prevent and treat severe COVID-19 in hamsters. This is the first time the nanobodies–which are similar to monoclonal antibodies but smaller in size, more stable and cheaper to produce–were tested for inhalation treatment against coronavirus infections in a pre-clinical model.

The scientists showed that low doses of an aerosolized nanobody named Pittsburgh inhalable Nanobody-21 (PiN-21) protected hamsters from the dramatic weight loss typically associated with severe SARS-CoV-2 infection and reduced the number of infectious virus particles in the animals’ nasal cavities, throats and lungs by a million-fold, compared to placebo treatment with a nanobody that doesn’t neutralize the virus.

By using an inhalation therapy that can be directly administered to the infection site–the respiratory tract and lungs–we can make treatments more efficient,” said co-senior author Yi Shi, Ph.D., assistant professor of cell biology at Pitt. “We are very excited and encouraged by our data suggesting that PiN-21 can be highly protective against severe disease and can potentially prevent human-to-human viral transmission.

Previously, Shi and colleagues discovered a large repertoire of over 8,000 high-affinity SARS-CoV-2 nanobodies. From this repertoire, the scientists selected an ultrapotent nanobody (Nb21) and bioengineered it into a rimeric form to further maximize its antiviral activity. The resulting PiN-21 is by far the most potent antiviral nanobody that has been identified, according to the researchers’ review of published studies.

Source: https://www.eurekalert.org/