APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI.
<h4>Background</h4>Impaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer's disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4, a strong genetic risk fac...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0316808 |
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| author | Aravind Lathika Rajendrakumar Konstantin G Arbeev Olivia Bagley Matt Duan Anatoliy I Yashin Svetlana Ukraintseva Alzheimer’s Disease Neuroimaging Initiative |
| author_facet | Aravind Lathika Rajendrakumar Konstantin G Arbeev Olivia Bagley Matt Duan Anatoliy I Yashin Svetlana Ukraintseva Alzheimer’s Disease Neuroimaging Initiative |
| author_sort | Aravind Lathika Rajendrakumar |
| collection | DOAJ |
| description | <h4>Background</h4>Impaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer's disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4, a strong genetic risk factor for AD.<h4>Methods</h4>We analyzed data on 1,509 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using multivariate linear regression models. The outcomes were rank-normalized hypometabolic convergence index (HCI), statistical regions of interest (SROI) for AD, and mild cognitive impairment (MCI). Marginal mean estimates for infections, stratified by APOE4 carrier status, were then computed.<h4>Results</h4>Prior infections were associated with greater HCI [β = 0.15, 95% CI: 0.03, 0.27, p = 0.01]. The combined effects of infections and APOE4 carriers on HCI levels were significantly greater than either variable alone. Among APOE4 carriers, the estimated marginal mean was 0.62, rising to 0.77, with infections (p<0.001), indicating an interaction effect. Carriers with multiple infections showed greater hypometabolism (higher HCI), with an estimate of 0.44 (p = 0.01) compared to 0.11 (p = 0.08) for those with a single infection, revealing a dose-response relationship. The estimates for the association of infections with SROI AD and SROI MCI were β = -0.01 (p = 0.02) and β = -0.01 (p = 0.04), respectively.<h4>Conclusion</h4>Our findings suggest that infections and APOE4 jointly contribute to brain glucose hypometabolism and AD pathology, supporting a "multi-hit" mechanism in AD development. |
| format | Article |
| id | doaj-art-93698d4f2eab4237ab978c5aa56d4013 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-93698d4f2eab4237ab978c5aa56d40132025-01-18T05:31:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031680810.1371/journal.pone.0316808APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI.Aravind Lathika RajendrakumarKonstantin G ArbeevOlivia BagleyMatt DuanAnatoliy I YashinSvetlana UkraintsevaAlzheimer’s Disease Neuroimaging Initiative<h4>Background</h4>Impaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer's disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4, a strong genetic risk factor for AD.<h4>Methods</h4>We analyzed data on 1,509 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using multivariate linear regression models. The outcomes were rank-normalized hypometabolic convergence index (HCI), statistical regions of interest (SROI) for AD, and mild cognitive impairment (MCI). Marginal mean estimates for infections, stratified by APOE4 carrier status, were then computed.<h4>Results</h4>Prior infections were associated with greater HCI [β = 0.15, 95% CI: 0.03, 0.27, p = 0.01]. The combined effects of infections and APOE4 carriers on HCI levels were significantly greater than either variable alone. Among APOE4 carriers, the estimated marginal mean was 0.62, rising to 0.77, with infections (p<0.001), indicating an interaction effect. Carriers with multiple infections showed greater hypometabolism (higher HCI), with an estimate of 0.44 (p = 0.01) compared to 0.11 (p = 0.08) for those with a single infection, revealing a dose-response relationship. The estimates for the association of infections with SROI AD and SROI MCI were β = -0.01 (p = 0.02) and β = -0.01 (p = 0.04), respectively.<h4>Conclusion</h4>Our findings suggest that infections and APOE4 jointly contribute to brain glucose hypometabolism and AD pathology, supporting a "multi-hit" mechanism in AD development.https://doi.org/10.1371/journal.pone.0316808 |
| spellingShingle | Aravind Lathika Rajendrakumar Konstantin G Arbeev Olivia Bagley Matt Duan Anatoliy I Yashin Svetlana Ukraintseva Alzheimer’s Disease Neuroimaging Initiative APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI. PLoS ONE |
| title | APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI. |
| title_full | APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI. |
| title_fullStr | APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI. |
| title_full_unstemmed | APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI. |
| title_short | APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI. |
| title_sort | apoe4 and infectious diseases jointly contribute to brain glucose hypometabolism a biomarker of alzheimer s pathology new findings from the adni |
| url | https://doi.org/10.1371/journal.pone.0316808 |
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