Herpes and Alzheimer's

genomeweb |  Based on network analyses spanning transcriptomic, genomic, and proteomic features of brain viromes in aging individuals with or without late-onset Alzheimer's disease (AD), a team led by researchers at the Icahn School of Medicine and Arizona State University has proposed potential ties between human herpesvirus (HHV) infection, amyloid precursor protein (APP) metabolism, and AD.

"This study represents a significant advancement in our understanding of the plausibility of the pathogen hypothesis of Alzheimer's," corresponding author Joel Dudley, a genetics, genomic sciences, and multi-scale biology researcher affiliated with the Icahn School of Medicine and the ASU-Banner Neurodegenerative Disease Research Center, said in a statement.

As they reported online today in Neuron, Dudley and his colleagues sequenced RNA in hundreds of postmortem brain samples, representing unaffected controls and preclinical AD cases, meaning symptom-free individuals with AD neuropathology. Their data revealed a dramatic over-representation of HHV-7 and HHV-6A strains in the preclinical AD endophenotype.

The team shored up this apparent association using data for individuals from additional cohorts of clinical AD cases and controls without AD pathology or symptoms. Network analyses based on whole-exome sequencing, liquid chromatography tandem mass spectrometry, and immunohistochemistry data, along with mouse model experiments, suggested that this association may stem from interactions between viral abundance, transcriptional regulators, and other modulators of APP metabolism.

Studies stretching back several decades have raised the possibility that microbial infections and the immune response mounted against them might contribute to the onset or progression of neurodegenerative conditions such as AD, the authors noted. Even so, they wrote, such research has been "suggestive of a viral contribution to AD, though findings offer little insight into potential mechanisms, and a consistent association with specific viral species has not emerged."