Fight to end Alzheimer's on The Longest Day

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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).

Using computational tools to analyze these large datasets, the researchers were able to generate a picture of the genetic, transcriptional, and molecular networks that underpin AD development and progression and how viruses are potentially involved.

They also found that multiple points overlapped between virus-host interactions and genes associated with Alzheimer's risk, and multiple viruses that impact Alzheimer's disease were found in DNA, RNA and proteins. "I don't think we can answer whether herpesviruses are a primary cause of Alzheimer's disease".

The American team found "unusually high" levels of two strains of human herpes virus 6A (HHV-6A) and human herpes virus 7 (HHV-7) in brains of Alzheimer's sufferers compared to those free of the disease.

Although the findings did not prove that the viruses directly cause its onset or progression, they have showed the viral DNA sequences and the activation of biological networks may interact with molecular, genetic and clinical aspects of Alzheimer's, according to the study.

The idea that infections earlier in life might somehow set the stage for Alzheimer's decades later has simmered at the edge of mainstream medicine for years. What they found is that Alzheimer's biology is likely impacted by a complex constellation of viral and host genetic factors, adding that they identified specific testable pathways and biological networks.

The new research is the fruitful result of close working relationships among researchers from Arizona State University, Banner, Mount Sinai and other research organizations, as well as public-private partnerships in AMP-AD. Dudley has met researchers at conferences who have confided in him that they have also collected data implicating pathogens in the disease but that they have been too scared to publish-for fear that they will be ostracized by the Alzheimer's community.

Researchers at the Icahn School of Medicine in NY and Arizona State University in Tempe conducted RNA sequencing on data from 3 brain banks to evaluate differential viral abundance in AD. HHV-7 infects more than 80 percent of infants, often causing a rash.

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The nature and significance of viruses and other pathogens in the brain are now hot topics in neuroscience, though the exploration is still in its early stages. "And if viral infections are playing a part, they are not the sole actor".

And those with more advanced disease had more virus in their brains.

"The title of the talk that I usually give is, 'I Went Looking for Drug Targets and All I Found Were These Lousy Viruses, '" explains Joel Dudley, co-senior author on the study.

"This analysis allowed us to identify how the viruses are directly interacting with or coregulating known Alzheimer's genes".

Childhood viruses that infect nearly everyone and lie dormant in the body for life might be involved in Alzheimer's disease, researchers reported Thursday.

Even so, the study offers strong evidence that viral infections can influence the course of Alzheimer's, Hodes says. Now, the main theory is that sticky brain-clogging plaques are the culprit.

While the current findings are more specific, they do not provide evidence to change how risk and susceptibility are assessed, nor the diagnosis and treatment of Alzheimer's, the authors said. "We are excited about the chance to capitalize on this approach to help in the scientific understanding, treatment, and prevention of Alzheimer's and other neurodegenerative diseases".

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