Irish 'breakthrough of the century' on Alzheimer's disease

Maricruz Casares
Junio 24, 2018

The researchers confirmed their findings with sequencing samples collected by other brain banks, including the Mayo Clinic in Florida and the Religious Orders Study at Rush University in Chicago, observing a persistent abundance of HHV-6A and HHV-7 among Alzheimer's disease patients in those cohorts, too.

Researchers have been attempting to identify links to viruses and, ultimately, new treatment strategies. "But we were able to perform a more sophisticated computational analysis using multiple levels of genomic information measured directly from affected brain tissue".

"While these findings do potentially open the door for new treatment options to explore in a disease where we've had hundreds of failed trials, they don't change anything that we know about the risk and susceptibility of Alzheimer's disease or our ability to treat it today", Gandy said. I don't think we can answer whether herpesviruses are a primary cause of AD. "But what's clear is that they're perturbing and participating in networks that directly underlie Alzheimer's pathophysiology". In a paper published online on June 21st, also in Neuron, Moir and colleagues reported that amyloid beta peptides bind to and entrap HSV-1 and HHV-6, thereby helping to protect against infection.

"It was really striking", says Sam Gandy, a co-author who is a Mount Sinai neurologist and amyloid expert. "Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also hard to resolve".

For the new study, which was broadly created to map and compare genetic, transcriptional, and protein networks underlying AD, the team analyzed whole exome DNA and RNA sequencing data from 622 brain donors with early- and later-stage clinical and neuropathological features of AD, and another 322 brains from donors without the disease, generated through the National Institutes of Health (NIH)-sponsored Accelerated Medicines Partnership for Alzheimer's Disease (AMP-AD). Sure enough, the animals developed more of those amyloid plaques.

The goal was to identify new targets for drugs.

"This work identifies a unique way to enhance the localised nutrients of the brain". Dudley is a member of the ASU-Banner Neurodegenerative Disease Research Center.

Most people have antibodies that indicate they have been infected with HHV-7, for instance, yet few develop Alzheimer's.

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"We didn't set out to find what we found".

Prof Nolan pointed out that the study included 27 patients in total, including two comparison groups who were given macular carotenoids only. "It could be that things are not as binary as we thought, that viruses act one way and genes another". "We were looking for genes that were dysregulated during the progression of Alzheimer's disease". "Viruses were the last thing we were looking for", Dudley says.

"We were able to build a social network of the virus and the host genes, to see who is friends with who", Dudley said.

Prof Dudley said: "We didn't have a horse in this virus race whatsoever".

The networks described suggest that the hallmarks of AD may arise as collateral damage caused by the brain's response to viral insult.

Currently, no effective prevention or treatment exists for this progressive deterioration of brain tissue, memory and identity, but researchers are hopeful that new, better treatments can emerge as a result of their work. Their data analyses and subsequent studies in experimental mice found that the HHV-6A virus effectively suppressed miR-155, leading to altered levels of Aβ and amyloid plaque density in vivo. "And if viral infections are playing a part, they are not the sole actor". "This is is also consistent with the contribution of viral perturbation in driving the preclinical AD transcriptional phenotype, given that our prioritization of miR-155 was informed by findings in the preclinical AD networks".

Blue Cross and the Alzheimer's Association hope the purple displays not only bring awareness to the disease, but also remind MI residents of the importance of brain health.

They say, "It'll be a day filled with sweet visuals of local seniors engaging with the community to support their peers affected by Alzheimer's".

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