Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging
Abstract Background Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of AD, possibly instigating amyloid-beta (Aβ) accumulation decades before the onset of clinical symptoms. However, human in vivo evidence linking HSV-1 infection to AD pathology is lac...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-024-01437-4 |
| _version_ | 1797219990254911488 |
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| author | Jose L. Cantero Mercedes Atienza Isabel Sastre María Jesús Bullido |
| author_facet | Jose L. Cantero Mercedes Atienza Isabel Sastre María Jesús Bullido |
| author_sort | Jose L. Cantero |
| collection | DOAJ |
| description | Abstract Background Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of AD, possibly instigating amyloid-beta (Aβ) accumulation decades before the onset of clinical symptoms. However, human in vivo evidence linking HSV-1 infection to AD pathology is lacking in normal aging, which may contribute to the elucidation of the role of HSV-1 infection as a potential AD risk factor. Methods To shed light into this question, serum anti-HSV IgG levels were correlated with 18F-Florbetaben-PET binding to Aβ deposits and blood markers of neurodegeneration (pTau181 and neurofilament light chain) in cognitively normal older adults. Additionally, we investigated whether associations between anti-HSV IgG and AD markers were more evident in APOE4 carriers. Results We showed that increased anti-HSV IgG levels are associated with higher Aβ load in fronto-temporal regions of cognitively normal older adults. Remarkably, these cortical regions exhibited abnormal patterns of resting state-functional connectivity (rs-FC) only in those individuals showing the highest levels of anti-HSV IgG. We further found that positive relationships between anti-HSV IgG levels and Aβ load, particularly in the anterior cingulate cortex, are moderated by the APOE4 genotype, the strongest genetic risk factor for AD. Importantly, anti-HSV IgG levels were unrelated to either subclinical cognitive deficits or to blood markers of neurodegeneration. Conclusions All together, these results suggest that HSV infection is selectively related to cortical Aβ deposition in normal aging, supporting the inclusion of cognitively normal older adults in prospective trials of antimicrobial therapy aimed at decreasing the AD risk in the aging population. |
| first_indexed | 2024-04-24T12:42:25Z |
| format | Article |
| id | doaj.art-3981710a3aa949b989ce051f621a8ca1 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-04-24T12:42:25Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-3981710a3aa949b989ce051f621a8ca12024-04-07T11:10:57ZengBMCAlzheimer’s Research & Therapy1758-91932024-04-0116111110.1186/s13195-024-01437-4Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal agingJose L. Cantero0Mercedes Atienza1Isabel Sastre2María Jesús Bullido3Laboratory of Functional Neuroscience, Pablo de Olavide UniversityLaboratory of Functional Neuroscience, Pablo de Olavide UniversityCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos IIICentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos IIIAbstract Background Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of AD, possibly instigating amyloid-beta (Aβ) accumulation decades before the onset of clinical symptoms. However, human in vivo evidence linking HSV-1 infection to AD pathology is lacking in normal aging, which may contribute to the elucidation of the role of HSV-1 infection as a potential AD risk factor. Methods To shed light into this question, serum anti-HSV IgG levels were correlated with 18F-Florbetaben-PET binding to Aβ deposits and blood markers of neurodegeneration (pTau181 and neurofilament light chain) in cognitively normal older adults. Additionally, we investigated whether associations between anti-HSV IgG and AD markers were more evident in APOE4 carriers. Results We showed that increased anti-HSV IgG levels are associated with higher Aβ load in fronto-temporal regions of cognitively normal older adults. Remarkably, these cortical regions exhibited abnormal patterns of resting state-functional connectivity (rs-FC) only in those individuals showing the highest levels of anti-HSV IgG. We further found that positive relationships between anti-HSV IgG levels and Aβ load, particularly in the anterior cingulate cortex, are moderated by the APOE4 genotype, the strongest genetic risk factor for AD. Importantly, anti-HSV IgG levels were unrelated to either subclinical cognitive deficits or to blood markers of neurodegeneration. Conclusions All together, these results suggest that HSV infection is selectively related to cortical Aβ deposition in normal aging, supporting the inclusion of cognitively normal older adults in prospective trials of antimicrobial therapy aimed at decreasing the AD risk in the aging population.https://doi.org/10.1186/s13195-024-01437-4Herpes simplex virusAgingAmyloid PETNeurodegenerationAlzheimer’s diseaseAmyloid-beta plaques |
| spellingShingle | Jose L. Cantero Mercedes Atienza Isabel Sastre María Jesús Bullido Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging Alzheimer’s Research & Therapy Herpes simplex virus Aging Amyloid PET Neurodegeneration Alzheimer’s disease Amyloid-beta plaques |
| title | Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging |
| title_full | Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging |
| title_fullStr | Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging |
| title_full_unstemmed | Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging |
| title_short | Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging |
| title_sort | human in vivo evidence of associations between herpes simplex virus and cerebral amyloid beta load in normal aging |
| topic | Herpes simplex virus Aging Amyloid PET Neurodegeneration Alzheimer’s disease Amyloid-beta plaques |
| url | https://doi.org/10.1186/s13195-024-01437-4 |
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