In a recent PET study with “unexpected” results, patients infected with herpes had fewer signs of brain deposits associated with Alzheimer’s disease than uninfected patients, a group in France has reported.
The finding is from an analysis of data from 182 patients at risk of cognitive decline, with the researchers offering two possible explanations for the association.
“Two possible explanations for these associations should be considered, either a modified immune response in [herpes simplex virus 1] infected subjects promoting the clearance of amyloid deposits or a selection bias related to the exclusion of participants with baseline dementia,” noted lead author Morgane Linard, MD, PhD, of the University of Bordeaux, and colleagues. The study was published January 18 in Scientific Reports.
The accumulation of brain amyloid deposits is a mechanism underlying Alzheimer’s disease, with amyloid PET scans used to diagnose the disease. A number of in vitro and animal studies have found that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits and loss of neurons, the authors explained. However, no studies to date have analyzed these associations in humans, they noted.
To address the knowledge gap, the group identified 182 out of 1,680 participants in an Alzheimer’s disease study in France and Monaco who had both PET scans and HSV-1 blood tests available. The median age of the group was 74 years old. Among the group, 85% were infected with HSV-1 and 43% had positive amyloid PET scans, based on regional standard uptake value ratios (SUVR) of F-18 florbetapir radiotracer.
According to the analysis, participants infected by HSV-1 tended to have a lower cortical SUVR on PET than uninfected participants (p = 0.06). Also, infected participants suspected to reactivate HSV-1 more frequently also had lower cortical SUVR (p = 0.03) for amyloid than uninfected participants.
“This result is unexpected given the various studies showing that HSV-1 inoculation leads to [beta amyloid] accumulation in vitro and in animals,” the group wrote.
In terms of explaining the results, the authors suggested that HSV-1 infection may lead to changes in the immune response within the central nerve system that promote the clearance of amyloid deposits.
Conversely, including only participants at risk of cognitive decline and with few objectifiable cognitive symptoms could have led to the selection of infected subjects with fewer underlying amyloid pathology, they wrote.
In either case, the results are intriguing and call for further investigation, the group noted.
“Overall, discrepancies between these results and those obtained in vitro, in animals or in humans when analyzing intrathecal synthesis of anti-HSV [immunoglobulin G] will require additional investigations, especially at different stages of the disease and in larger samples,” the researchers concluded.
The full study is available here.
