title: Blood brain barrier impairment is associated with cerebrospinal fluid markers of neuronal damage in HIV-positive patients.
abstract: Blood brain barrier impairment occurs early in the course of infection by HIV and it may persist in a subset of patients despite effective antiretroviral treatment. We tested the hypothesis that HIV-positive patients with dysfunctional blood brain barrier may have altered biomarkers of neuronal damage. In adult HIV-positive highly active antiretroviral treatment (HAART)-treated patients (without central nervous system infections and undergoing lumbar punctures for clinical reasons) cerebrospinal fluid albumin to serum ratios (CSAR), total tau, phosphorylated tau, 1-42 beta amyloid, and neopterin were measured. In 101 adult patients, cerebrospinal fluid-to-serum albumin ratios were 4.8 (3.7-6.1) with 12 patients (11.9%) presenting age-defined impaired blood brain barrier. A significant correlation was observed between CSAR and total tau (p = 0.005), phosphorylated tau (p = 0.008), and 1-42 beta amyloid (p = 0.040). Patients with impaired blood brain barrier showed significantly higher total tau (201.6 vs. 87.3 pg/mL, p = 0.010), phosphorylated tau (35.3 vs. 32.1 ng/mL, p = 0.035), and 1-42 beta amyloid (1134 vs. 830 pg/mL, p = 0.045). Despite effective antiretroviral treatment, blood brain barrier impairment persists in some HIV-positive patients: it is associated with markers of neuronal damage and it was not associated with CSF neopterin concentrations.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10149, Torino, Italy. andrea.calcagno@unito.it.
authors.forename: A
authors.initials: A
authors.lastname: Calcagno
authors.affiliation: Unit of neurology, Ospedale Maria Vittoria, ASLTO2, Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Atzori
authors.affiliation: Laboratory of Immunology, Ospedale Maria Vittoria, ASLTO2, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Romito
authors.affiliation: Unit of neurology, Ospedale Maria Vittoria, ASLTO2, Torino, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Vai
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10149, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Audagnotto
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10149, Torino, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Stella
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10149, Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Montrucchio
authors.affiliation: Unit of neurology, Ospedale Maria Vittoria, ASLTO2, Torino, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Imperiale
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10149, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10149, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bonora
mesh_terms: D000328:Adult; D000418:Albumins / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000134:cerebrospinal fluid; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D000418:Albumins; D016229:Amyloid beta-Peptides; D019380:Anti-HIV Agents; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019798:Neopterin
keywords: Albumin ratio; Blood brain barrier; Neopterin; Phosphorylated tau; Tau