Background
Elevated levels of inflammation and neurodegeneration in the brain and periphery are associated with worse brain health outcomes in persons without HIV (PWoH). People with HIV (PWH) may have greater peripheral inflammation and neurodegeneration that may cause elevated brain inflammation and white matter changes. Brain inflammation can be measured using diffusion-based spectral imaging (DBSI) derived global cellularity (GC) which is associated with activated microglia. This study examines the association between plasma measures of inflammation and neurodegeneration and brain measures of inflammation in PWH.
Methods
227 PWH (77% male) and 45 PWoH (56% male) age≥30 underwent brain imaging and blood draw for inflammatory and neurodegeneration markers. The isotropic portion of the diffusion weighted signal attributed to cellularity was extracted globally and processed using established pipelines. Plasma (sCD163, sCD14, glial fibrillary acidic protein [GFAP], and neurofilament light chain [NfL]) biomarkers were quantified. CD14+CD16-, CD14+CD16+ and CD14-CD16+ monocyte cell populations were also quantified. GC was first compared with age. GC was then compared to plasma markers and monocytes using regression models with age and sex included as covariates.
Results
PWH had a significantly higher GC (p<0.001) than PWoH. Increasing age was significantly associated with increased GC in PWH (p<0.001) but not PWoH. Higher plasma sCD163 was associated with lower GC (p<0.05) in PWH. In PWoH, elevated CD14+CD16+ monocytes were associated with lower GC (p<0.001) while elevated plasma sCD163 was associated with higher GC (p<0.01). Both plasma GFAP and NfL were not associated with any changes in GC.
Conclusions
Altered levels of plasma inflammatory marker sCD163 and inflammatory CD14+CD16+ monocytes were associated with changes in brain inflammation in PWH and PWoH. However, plasma markers of neurodegeneration (NfL and GFAP) showed no association with central inflammation. The results for PWH align with the CD14+CD16+ monocytes being inflammatory and the sCD163 being anti-inflammatory while the results in PWoH display opposite trends. This suggests that DBSI GC may be sensitive to detecting central inflammatory processes happening specifically in PWH, but not PWoH. This could also suggest that plasma sCD163 and CD14+CD16+ monocytes may have different inflammatory process in PWH than PWoH. Peripheral markers of inflammation and monocytes may provide better insight into or predict brain inflammation in PWH.
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