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."
