The Influence of Blood Brain Barrier Permeability on CSF-To-Serum Ratios of Neurobiomarkers in People With HIV.

People with HIV (PWH) have a higher risk of central nervous system (CNS) diseases and a timely differential diagnosis may be essential for patient management. Cerebrospinal fluid (CSF) biomarkers have proven effective in diagnosing neuronal and astrocyte involvement in neurological disorders, but the invasiveness of this method makes it difficult to obtain results; thus, easy-to-obtain matrices (e.g., plasma) have to be analysed. Consequently, the aim of this study was to quantify biomarkers in both serum and CSF with different kits, correlating levels obtained in the two matrices and understanding their impact on blood brain barrier (BBB) permeability. CSF and serum from PWH were analysed through Single Molecule Array (Simoa SR-X, Quanterix). We measured markers of neuronal damage (NfL, tau, ptau), β-amyloid peptides (Aβ and Aβ), signalling and neuronal plasticity (BDNF), astrocyte activation (GFAP), ubiquitin-proteasome involvement (UCH-L1), and programmed death ligand-1 (PD-L1). BBB permeability was assessed through CSF-to-serum albumin ratio (CSAR). We included 286 samples: median age was 42.1 years (30.6-51), 69.2% were male. Median CSAR was 5.4 (3.9-7.3). We observed statistically significant correlations for all serum/CSF pairs, but rho values > 0.5 for tau, p-tau, GFAP, Aβ and Aβ only, when using different kits. NfL CSF-to-plasma ratios were higher in participants with higher CSAR (p = 0.0000016), with a higher ratio in participants with age-adjusted abnormal BBB (n = 34 for intact BBB and n = 66 for altered BBB, p = 0.001). We observed an average-to-high correlation between serum and CSF biomarkers in PWH, suggesting the possible use of serum levels for assessing CNS involvement: it is the first time that BBB permeability was found to influence such correlations.