Researchers at the NIH used RNA-Seq cells from skin and blood to study the underlying mechanisms in DIHS/DRESS and identified both HHV-6 and JAK-STAT pathways as potential targets. Central memory CD4+T cells were enriched with HHV-6B.
NINDS/NIH investigators find very little HHV-6 RNA or DNA in either Alzheimer’s or control brains
A team led by Steven Jacobson, PhD at NINDS analyzed RNA-seq datasets from 901 brains, and found only 1.2% of Alzheimer’s patients and 0.4% of controls positive for HHV-6 RNA. They also found HHV-6 DNA in less than 4% of samples tested by ddPCR.
The debate continues over RNA-seq analysis of HHV-6A in Alzheimer’s
Two groups have challenged the widely-publicized 2018 study in 2018, that found increased HHV-6A & 7 abundance and an association with clinical and pathology scores in Alzheimer’s. The topic has become the focus vigorous debate.
HHV-6A induces dysregulation of autophagy in neurons and astrocytoma cells, increasing beta-amyloid and tau
Building on their prior work, an Italian team has shown that HHV-6A is able to induce dysregulation of autophagy in neurons and astrocytoma cells, increasing amyloid beta and tau production.
HHV-6A activates microglia and increases Aβ and tau expression
HHV-6A infection of microglia cells increases inflammatory markers and Aβ and tau expression dramatically, supporting the hypothesis that plaque development in Alzheimer’s disease may be an innate immune response to pathogens
HHV-6B induces ER stress in primary monocytes, impairing their survival and differentiation into dendritic cells
Investigators propose that the induction of endoplasmic reticulum stress, likely exacerbated by autophagy inhibition, could contribute to the immune suppression induced by HHV-6B in exanthem subitem patients.
Differential gene expression pattern shared in herpesviruses, Alzheimer’s & Parkinson’s patients
Researchers from GlaxoSmithKline found a significant overlap in differentially expressed genes shared by those with herpesvirus infections, Alzheimer’s and Parkinson’s. On the other hand, there was no significant overlap between herpesviruses and Type 2 diabetes or Huntington’s disease.
Herpesvirus acquires protein corona that facilitates the formation of Alzheimer’s plaques
Swedish researchers report that viruses interact with proteins to form a coating or protein corona that facilitates the formation of amyloid plaque, supporting previous findings by Harvard’s Rudy Tanzi and Robert Moir.
Single-cell transcriptomic analysis of Alzheimer’s brains showed early changes that are highly cell-type specific with APOE strongly upregulated in the microglia
MIT examined transcription across tens of thousands of individual cells in both Alzheimer’s and healthy brains and found APOE strongly upregulated in the microglia and perturbation in myelination-related processes in multiple cell types including oligodendrocytes.
Could autophagy dysregulation link neurotropic viruses to Alzheimer’s disease?
The cellular housekeeping function of autophagy may play a role in Alzheimer’s as dysfunction could result in the accumulation of amyloid. HHV-6A, HHV-6B and HSV1 can infect central nervous system cells and dysregulate autophagy.
Herpesviruses may reduce NK cell cytotoxicity in Alzheimer’s
MS patients with a particular haplotype on natural killer cells are more susceptible to HHV-6A infection. Similarly, HHV-6A/B may contribute to Alzheimer’s by utilizing a specific NK cell inhibitory receptor to disrupt the ability of NK cells to clear infected cells.
HHV-6 small non-coding RNA proposed as an indicator of an early stage of HHV-6 reactivation
German investigators have identified a marker for what they believe is the earliest stage of viral reactivation, or “transactivation” marked by transcription of several viral small non-coding RNAs in the absence of detectable viral replication. The group believes that these viral small RNAs could be developed as biomarkers.
Biospecimen Repositories for Alzheimer’s Disease
NIH NeuroBioBank (brain tissues from various neurological diseases) BrainNet Europe – 19 brain banks in 11 European countries UK Brain Banks Network Australian Brain Bank Network – accepts requests from outside Australia
Private funding available for Alzheimer’s research
Alzheimer’s Disease Research Grants–Private sources of funds
National Institute on Aging encourages grant proposals on HHV-6A & HHV-7 in Alzheimer’s
NIH leaders of the National Institute on Aging (NIA) encouraged investigators with experience in virology and infectious disease to apply for funding to study Alzheimer’s disease. The encouragement came at a workshop held at the Alzheimer’s Association International Conference in Chicago on July 22nd.
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