Eyes Provide Peek at Alzheimer’s Disease Risk

Protein deposits in retina and brain appear to parallel possible neurodegeneration, an insight that might lead to easier, quicker detection. Amyloid plaques are protein deposits that collect between brain cells, hindering function and eventually leading to neuronal death. They are considered a hallmark of Alzheimer’s disease (AD), and the focus of multiple investigations designed to reduce or prevent their formation, including the nationwide A4 study.

But amyloid deposits may also occur in the retina of the eye, often in patients clinically diagnosed with AD, suggesting similar pathologies in both organs. In a small, cross-sectional study, a team of researchers, led by scientists at University of California San Diego School of Medicine, compared tests of retinal and brain amyloids in patients from the A4 study and another study (Longitudinal Evaluation of Amyloid Risk and Neurodegeneration) assessing neurodegeneration risk in persons with low levels of amyloid.

Like the proverbial “windows to the soul,” the researchers observed that the presence of retinal spots in the eyes correlated with brain scans showing higher levels of cerebral amyloid. The finding suggests that non-invasive retinal imaging may be useful as a biomarker for detecting early-stage AD risk.

Amyloid deposits tagged by curcumin fluoresce in a retinal scan.

This was a small initial dataset from the screening visit. It involved eight patients,” said senior author Robert Rissman, PhD, professor of neurosciences at UC San Diego School of Medicine. “But these findings are encouraging because they suggest it may be possible to determine the onset, spread and morphology of AD — a preclinical diagnosis — using retinal imaging, rather than more difficult and costly brain scans. We look forward to seeing the results of additional timepoint retinal scans and the impact of solanezumab (a monoclonal antibody) on retinal imaging. Unfortunately we will need to wait to see and analyze these data when the A4 trial is completed.”

The findings published in the journal Alzheimer’s & Dementia.

https://ucsdnews.ucsd.edu/

Alzheimer’s May Be Caused By Dental Infection

In a new study scientists reveal yet another reason to keep up on dental hygiene. Bacteria that cause a common yet largely preventable gum infection may also play a role in Alzheimer’s disease. The discovery also offers hope for a treatment that could slow neurodegeneration.

There were many clues in the [features of Alzheimer’s disease] that an infection is at work,” said Casey Lynch, an entrepreneur and co-founder of Cortexyme, a biotech company headquartered at the Verily Life Sciences campus in South San Francisco, who led the new research. “Many of the genetic risk factors for Alzheimer’s are related to immune system function,” she added, which suggests “immune system dysfunction might put people more at risk.

Alzheimer’s disease, an irreversible and progressive brain disorder that leads to memory loss and diminished thinking skills, affects at least 5 million Americans. Clumps of a brain protein known as amyloid plaques are a hallmark sign of the disease. Billions of research dollars have gone towards finding a treatment that destroys these mind-robbing masses. But there’s still no cure.

Not enough people are asking what is upstream of the plaques … and [brain] inflammation,” said Lynch, who has a background in Alzheimer’s research and was frustrated by the string of failed therapies for the disease. Nearly six years ago, Lynch received a call from Stephen Dominy, a psychiatrist at the University of California, San Francisco, who had studied the link between HIV and dementia.

I think I’ve found a bacterial cause of Alzheimer’s,” Dominy, who co-founded Cortexyme with Lynch and now serves as the company’s Chief Scientific Officer, told her. Dominy had spent about 15 years searching for infections that might lead to Alzheimer’s until evidence for a bacterium known as P. gingivalis became “undeniable,” according to Lynch. P. gingivalis causes periodontitis, an infection that destroys the gums and can lead to tooth loss.

When the team examined the brains and cerebrospinal fluid of Alzheimer’s patients, they found DNA from the bacterium. They also discovered bacterial enzymes called gingipains that destroy brain cells were present, too. And when they watched P. gingivalis infections play out in mice, it triggered neurodegeneration in the hippocampus, a brain structure central to memory. It also led to Alzheimer’s hallmark amyloid beta plaque production and inflammation, the researchers discovered.

The scientists then designed and created a new molecule that blocks the gingipain enzymes. The antibiotic reduced the amount of bacteria in infected mice and stopped the formation of amyloid beta plaques while reducing inflammation, the team reports Wednesday in the journal Science Advances.

Source: https://www.discovermagazine.com/