NIH Study Debunks Long-Held Symptomatic Herpes-Alzheimer's Connection
Researchers at the NIH’s National Institute on Aging found that symptomatic herpes viruses were associated with neurological and cognitive symptoms, but there was no evidence to support a long-held theory that they are linked to Alzheimer’s disease.
The participants who were diagnosed with herpes had higher cognitive scores at the beginning of their participation but demonstrated greater longitudinal decreases in attention performance. The study did not find a link between herpes virus infection and the volume of total brain or gray matter, or in areas associated with Alzheimer’s disease. The authors published their research in the journal Neurology.
The researchers, led by Keenan Walker, Ph.D., analyzed data from 1,009 participants in the Baltimore Longitudinal Study of Aging (BLSA). Of them, 98% were cognitively normal at baseline MRI. These people received comprehensive cognitive evaluations starting between 1984 and 1993 and 3T MRI scans began in 2009 and 2010.
“We did not find evidence that herpetic infection is associated with measures of Alzheimer’s-specific disease processes, including brain volumes vulnerable to atrophy in Alzheimer’s disease, verbal memory performance and a measure of amyloid plaque burden,” Walker told MedPage Today.
Plasma biomarkers were also tested at the time of the first MRI. The participants made study visits biannually until 2005, then every one to four years depending on their age.
Of the total participants, 119 had a record of symptomatic herpes infection. These infections were linked to longitudinal decreases in white matter volume, particularly in the temporal lobe. Being treated with antivirals slowed the declines in occipital white matter.
Just what Causes Alzheimer's Disease?
The causes of Alzheimer’s disease are not fully understood. There are clear associations with the accumulation of abnormal proteins in the brain, beta-amyloid and tau. There is also clear evidence of neuroinflammation, and there appears to be evidence of immune dysfunction in microglia, a type of immune cell found within the brain.
One recurring theory is that herpes viruses, which are responsible for cold sores, genital herpes and other infections, might cause Alzheimer’s disease.
For example, a 2020 study in laboratory tests of human skin cells reprogrammed into neurons that were then infected with herpes simplex virus (HSV-1) resulted in the accumulation of beta-amyloid much like the plaques seen in Alzheimer’s patients. However, HSV-1 infections are very common, so it’s unknown why the virus would trigger Alzheimer’s only in some people.
Other studies found human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) in the brain tissue samples collected during autopsies in Alzheimer’s patients. The levels were up to twice as high as those found in non-Alzheimer's samples. It’s possible that the higher viral levels are related to overall immune dysfunction, rather than the higher viral levels causing Alzheimer’s.
Research has also suggested a combination of HSV-1 and the APOE4 gene might increase Alzheimer’s susceptibility. APOE4 is the most common genetic variant associated with Alzheimer’s disease, although it is not the only one.
The varicella-zoster virus study found that when the virus infects neurons, it triggers an inflammatory response marked by a surge of cytokine secretion. This stimulates herpes simplex viruses, which are typically dormant in the brain. The researchers theorized that now that both viruses are active in the brain, it sparks neuroinflammation, leading to the formation of beta-amyloid plaques and neuronal deterioration.
Walker wrote, “An infectious origin of Alzheimer’s disease has received renewed attention, with particular focus on human herpes viruses and other inflammatory factors. However, the effect of these viruses on brain structure and cognition over time remain (sic) poorly understood, as do their effects on Alzheimer’s and neurodegeneration biomarkers.”