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Risk of developing cerebral ?-amyloid plaques with posttranslational modification among HIV-infected adults.

ABSTRACT: OBJECTIVES:Evidence of accelerated brain aging among HIV-infected adults argues for the increased risk of developing cerebral ?-amyloid (A?) plaques. We compared the frequency of A? plaque-bearing cases in our HIV cohort with that in a general cohort reported by Braak et al. We explored posttranslationally modified A? forms (N3pE, E22P, phospho-Ser8) in plaques and E22P-A? in the postmortem cerebrospinal fluid (CSF) in the HIV cohort. DESIGN:Clinicopathological study of HIV-infected adults. METHODS:To assess frontal A? plaque deposition, we conducted immunohistochemistry for generic A? (4G8) and three modified A? forms. We determined CSF E22P-A? levels by ELISA. RESULTS:We found 4G8-A? plaques in 29% of 279 HIV-infected cases. Within the age range of 31-70 years, the frequency of 4G8-A? plaque-bearing cases was higher in our HIV cohort (n?=?273) compared with the general cohort (n?=?1110) overall (29.3 vs. 25.8%) and across four age groups by decade (odds ratio 2.35, P?

SUBMITTER: Umlauf A

PROVIDER: S-EPMC6852888 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Risk of developing cerebral β-amyloid plaques with posttranslational modification among HIV-infected adults.

Umlauf Anya A Soontornniyomkij Benchawanna B Sundermann Erin E EE Gouaux Ben B Ellis Ronald J RJ Levine Andrew J AJ Moore David J DJ Soontornniyomkij Virawudh V

AIDS (London, England) 20191101 14

<h4>Objectives</h4>Evidence of accelerated brain aging among HIV-infected adults argues for the increased risk of developing cerebral β-amyloid (Aβ) plaques. We compared the frequency of Aβ plaque-bearing cases in our HIV cohort with that in a general cohort reported by Braak et al. We explored posttranslationally modified Aβ forms (N3pE, E22P, phospho-Ser8) in plaques and E22P-Aβ in the postmortem cerebrospinal fluid (CSF) in the HIV cohort.<h4>Design</h4>Clinicopathological study of HIV-infect ...[more]

PMID: 31688040

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Project description:Fatigue is a common symptom in the elderly and has also been associated with impaired cognition in older adults. Hence, we sought to explore the cross-sectional relationship between fatigue and cerebral ?-amyloid (A?) in 269 elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial. Standard uptake value ratios (SUVRs) were generated by [18F] florbetapir positron emission tomography (PET) using the cerebellum as a reference. Cortical-to-cerebellar SUVRs (cortical-SUVRs) were obtained using the mean signal from the frontal cortex, temporal cortex, parietal cortex, precuneus, anterior cingulate, and posterior cingulate. Other brain regions independently assessed were the anterior cingulate, anterior putamen, caudate, hippocampus, medial orbitofrontal cortex, occipital cortex, parietal cortex, pons, posterior cingulate, posterior putamen, precuneus, semioval center, and temporal cortex. Fatigue was defined according to two questions retrieved from the Center for Epidemiological Studies-Depression scale. Chronic fatigue was defined as meeting fatigue criteria at two consecutive clinical visits 6 months apart between study baseline and 1 year (visits were performed at baseline, 6 months and 1 year then annually). Cross-sectional associations between fatigue variables and cerebral A? were explored using fully adjusted multiple linear regression models. We found no statistically significant cross-sectional associations between fatigue assessed at the clinical visit closest to PET and A? in any brain region. Similarly, chronic fatigue was not significantly associated with A? load. Sensitivity analysis in subjects with a Clinical Dementia Rating of 0.5 showed that fatigue reported at the clinical visit closest to PET was, however, weakly associated with increased A? in the hippocampus (B-coefficient: 0.07, 95% CI: 0.01, 0.12, p?=?0.016). These preliminary results suggest that fatigue might be associated with A? in brain regions associated with Alzheimer's disease in subjects in the early stages of disease.

Project description:Background People living with HIV ( PLWH ) have an increased risk of myocardial infarction ( MI ). Changes in the gut microbiota that occur with chronic HIV infection could play a role in HIV -associated atherosclerosis. Choline, carnitine, betaine, and trimethylamine N-oxide are small molecules that are, in part, metabolized or produced by the gut microbiome. We hypothesized that these metabolites would be associated with carotid artery intima-media thickness and MI in PLWH . Methods and Results Carotid artery intima-media thickness was measured at baseline and at a median interval of 4 years in 162 PLWH from the SCOPE (Study of the Consequences of the Protease Inhibitor Era) cohort in San Francisco, CA . Separately, 105 PLWH (36 cases with type I adjudicated MI and 69 controls without MI ) were selected from the Center for AIDS Research Network of Integrated Clinical Systems, a multicenter clinic-based cohort. Controls were matched by demographics, CD 4 cell count, and duration of viral suppression. In the SCOPE cohort, higher carnitine levels had a significant association with presence of carotid plaque and greater baseline and progression of mean carotid artery intima-media thickness after adjusting for traditional cardiovascular disease risk factors. In the treated and suppressed subgroup, these associations with carnitine remained significant after adjustment for cardiovascular disease risk factors. In the Center for AIDS Research Network of Integrated Clinical Systems cohort, the risk of MI was significantly increased in subjects with carnitine levels in the highest quartile after adjustment for cardiovascular disease risk factors. Conclusions In PLWH , including the treated and suppressed subgroup, carnitine is independently associated with carotid artery intima-media thickness, carotid plaque, and MI in 2 separate cohorts. These results emphasize the potential role of gut microbiota in HIV -associated atherosclerosis and MI , especially in relation to carnitine metabolism.

Dataset Information

Risk of developing cerebral ?-amyloid plaques with posttranslational modification among HIV-infected adults.

Publications

Risk of developing cerebral β-amyloid plaques with posttranslational modification among HIV-infected adults.

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