| Publication Abstract Display | | Type: Poster | | Title: Distinct biomarker profiles of cognitive vulnerabilities in people with Human Immunodeficiency Virus (HIV). | | Authors: Bol K, Tang B, Sundermann EE, Riggs PK, Moore DJ | | Date: 02-05-2026 | | Abstract:Objective:
Despite effective antiretroviral therapy (ART), many people with HIV (PWH) show evidence of cognitive dysfunction. The neuropsychological profile among PWH is heterogeneous making it difficult to identify the biological mechanisms underlying these cognitive complications. To better understand these heterogenous profiles, multi-system biomarker panels provide the opportunity to disaggregate PWH into biologically informed subtypes. Neurology, cardiovascular, and inflammation biomarkers have been shown to be altered in PWH. However, it is not yet known whether distinct biomarker profiles spanning neurological, cardiovascular, and inflammatory systems map onto specific patterns of cognitive vulnerability in PWH, limiting our ability to identify biologically meaningful subtypes of impairment.
Participants and Methods:
Sixty-nine middle-aged PWH (45.6 ± 9.76 years, 79% male, 31% with viral suppression) from the National NeuroHIV Tissue Consortium participated in blood draws that measured proteins related to neurology, inflammation, and cardiovascular function with Olink Target 96 panels. Demographically corrected standardized T-scores from 15 neuropsychological tests, representing seven neuropsychological domains, were used to calculate domain-specific and a global deficit score with a domain deficit score of > 0.5 and a global deficit score ≥ 0.5 defining impairment per established standards. Associations of biomarkers to global and domain-specific cognitive impairment were assessed using linear regression with FDR correction applied.
Results:
Multiple plasma proteins were significantly associated with speed of information processing (SIP), working memory (WM), and motor impairment. Global and learning impairment were associated with inflammatory markers (Global: CXCL5, AXIN1; learning: TGFalpha). None of the biomarkers were associated with verbal, executive function, nor recall impairment. Nine significant biomarkers (e.g., LAT, MANF, CLEC1B, CXCL5, AXIN1, ST1A, MMP.1, CXCL1, CCL5) from the three panels were negatively associated with SIP impairment. Forty-three neurology and cardiovascular - but no inflammation - biomarkers were significantly associated with WM. Another set of forty-three biomarkers across the three panels were significantly associated with motor impairment. The most significant neurology and cardiovascular biomarkers were proteins associated with synaptic remodeling (e.g., UNC5C, ROBO2, PRTG) and endothelial and lymphatic activation (e.g., VCAM1, AXL-GAS6, LYVE1) and had positive associations. Conversely, inflammation biomarkers were negatively associated with motor impairment.
Conclusions:
Findings support strong links between plasma markers of maladaptive axon/synaptic signaling and endothelial/blood brain barrier disruption in WM and motor impairment. Motor impairment was even more strongly associated with neurovascular/lymphatic activation. In contrast, SIP showed associations with a protective profile with higher platelet/T-cell-LAT-CLEC1B signaling, possibly related to reduction of perivascular inflammation. CCL5 is consistently protective across domains. Overall, patterns argue against generalized peripheral inflammation and emphasize the importance of additional investigations into neurovascular and synaptic signaling pathways for diagnostic and therapeutic investigation of mechanisms underlying neurocognitive impairment among PWH. |
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