Virus World

Alzheimer’s disease (AD) is characterized pathologically by amyloid-beta (Aβ) deposition in brain parenchyma and blood vessels (as cerebral amyloid angiopathy (CAA)) and by neurofibrillary tangles of hyperphosphorylated tau. Compelling genetic and biomarker evidence supports Aβ as the root cause of AD. We previously reported human transmission of Aβ pathology and CAA in relatively young adults who had died of iatrogenic Creutzfeldt–Jakob disease (iCJD) after childhood treatment with cadaver-derived pituitary growth hormone (c-hGH) contaminated with both CJD prions and Aβ seeds. This raised the possibility that c-hGH recipients who did not die from iCJD may eventually develop AD. Here we describe recipients who developed dementia and biomarker changes within the phenotypic spectrum of AD, suggesting that AD, like CJD, has environmentally acquired (iatrogenic) forms as well as late-onset sporadic and early-onset inherited forms.

Although iatrogenic AD may be rare, and there is no suggestion that Aβ can be transmitted between individuals in activities of daily life, its recognition emphasizes the need to review measures to prevent accidental transmissions via other medical and surgical procedures. As propagating Aβ assemblies may exhibit structural diversity akin to conventional prions, it is possible that therapeutic strategies targeting disease-related assemblies may lead to selection of minor components and development of resistance. A small number of patients who received growth hormone preparations contaminated with seeds of the amyloid-beta protein developed Alzheimer’s disease many years after treatment.

Published in Nature Medicine (Jan. 29, 2024):

https://doi.org/10.1038/s41591-023-02729-2 

A new finding that even took the study’s authors by surprise lends support to the controversial idea that microbes play a role in Alzheimer’s disease. The research published June 21 in Neuron, found convincing signs that certain types of herpes virus may promote the complex process that leads to the disease that afflicts some 5.7 million Americans. The study points to the viruses as possible accomplices that drive disease progression but does not suggest that Alzheimer’s may begin after they are transmitted through casual contact. 

Joel Dudley, a geneticist and genomic scientist at the Icahn School of Medicine at Mount Sinai and senior author of the new paper, had not intended to investigate this theory when his lab began working on the newly published study in 2013. The plan he had made with colleagues was to identify possible new Alzheimer’s drug targets by looking at the molecular changes in the brain that occur during the disease. Thanks to a new NIH-led public-private partnership called the Accelerating Medicines Partnership Alzheimer's Disease (AMP-AD), the team had access to data from 876 brains—some healthy and some with early- or late-stage Alzheimer’s. They used DNA and RNA sequencing to parse out genetic differences between the groups as well as differences in how inherited genes were expressed or made into RNA. That’s when they started getting strange results. “The algorithms kept returning this pattern for viral biology,” Dudley says.

The team found more viral DNA in Alzheimer’s brains compared with healthy brains—specifically, high levels of DNA from human herpesvirus 6A (HHV-6A). RNA of both HHV-6A and HHV-7 were also higher in the Alzheimer’s brains than in healthy brains, and viral RNA levels tracked with the severity of clinical symptoms. HHV-6A is a usually symptom-less virus that infects people later in life. HHV-7 infects more than 80 percent of infants, often causing a rash.

Original research Published in Neuron on June 21, 2018

https://doi.org/10.1016/j.neuron.2018.05.023