A new review article, published in Frontiers in Aging Neuroscience, has offered fresh evidence in support of a link between the Herpes Simplex Virus 1 (HSV1) and Alzheimer’s disease (AD).
Of particular note in the review are new population data from Taiwan, in which more than 8,000 subjects with newly diagnosed HSV1 or HSV2 infection were compared to over 25,000 non-infected subjects over 10 years. Crucially, those with herpes infections were 2.5-times more likely to develop dementia than the control group. Even more interesting was the realisation that treatment with anti-herpes drugs reduced the likelihood of developing dementia by 10-fold.
This new review follows on from other recent findings in the field, including a study on more than 600 early-stage AD brains, which pinpointed more abundant strains of the herpes virus in AD brains compared to control brains. This research – published in Neuron – opens up the question of whether herpes could be a cause of the disease, or a resultant symptom.
That study suggested that the presence of the herpes virus in the brain could influence genes linked to increased AD risk. These include modulators of amyloid precursor protein (APP) metabolism, write the authors, such as induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1.
Originally the researchers were not aiming to look at a link between viruses and dementia, but – as lead author Ben Readhead described – the viruses “screamed out at us” while they were conducting research. Sam Gandy, a co-author of the study, explained more: “The viral genomes were detectable in about 30% of Alzheimer’s brains and virtually undetectable in the control group,” he said.
So surprised were the authors that they repeated the study twice, corroborating their findings each time. “We’ve tried to be conservative in our interpretation and replicated the results in three different brain banks, but we have to at least recognise that these diseased brains are carrying these viral genomes,” continued Dr Gandy.
While the extensive data from the study does offer plausibility to the notion that herpes genes in turn boost the activity of several known AD genes, several people have spoken out with cautious remarks. After all, at this stage the research has not been able to show that the virus actually causes the onset of AD; indeed, AD patients are more vulnerable to infection, which would support a contrasting theory that the elevated herpes levels come later as an effect of the disease.
“There are some families with mutations in specific genes who always get this disease. It’s difficult to square that with a viral aetiology. I’d urge an extremely cautious interpretation of these results,” stressed Professor John Hardy, a geneticist at University College London, UK.
What’s more, the particular herpes viruses highlighted (which incidentally do not cause one of the most common symptoms, cold sores) are carried in nearly everyone, and don’t typically cause any problems.
While clearly more needs to be done to clarify the questions left unanswered, as the authors conclude, for now the study offers elucidation of networks linking molecular, clinical, and neuropathological features with viral activity.