Markers of macrophage activation and axonal injury are associated with prospective memory in HIV-1 disease.
OBJECTIVE
To use clinical specimens to better understand the neuropathogenesis of prospective memory (ProM) functioning in persons with HIV-1 infection.


BACKGROUND
Emergent evidence suggests that HIV-1 is associated with impaired ProM, but the underlying neuropathophysiology of this deficit is not known.


METHODS
Thirty-five nondemented subjects with HIV-1 infection completed measures of both ProM (ie, memory for future intentions) and retrospective memory (RM; ie, memory for past episodes). A panel of biomarkers reflecting several possible neuropathogenic mechanisms of HIV was measured in plasma and cerebrospinal fluid, including HIV-1 RNA, total tau, monocyte chemoattractant protein-1 (MCP-1), soluble receptor for tumor necrosis factor type II, and fibroblast growth factor 1.


RESULTS
After controlling for antiretroviral therapy and CD4 lymphocyte count, higher levels of MCP-1 in plasma, and soluble receptor for tumor necrosis factor type II and tau in cerebrospinal fluid were associated with ProM, but not RM. Markers of astrocytosis, growth factor depletion, and HIV-1 replication did not predict either ProM or RM.


CONCLUSIONS
ProM impairment in HIV-1 may be dissociable from RM, perhaps reflecting specific neuropathogenic mechanisms of macrophage activation and axonal injury.
Woods
Steven Paul
SP
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. spwoods@ucsd.edu
Morgan
Erin E
EE
Marquie-Beck
Jennifer
J
Carey
Catherine L
CL
Grant
Igor
I
Letendre
Scott L
SL
D000328:Adult; D001369:Axons / Q000276:immunology / Q000473:pathology*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D000068800:Etanercept; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000097:blood / Q000134:cerebrospinal fluid; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007074:Immunoglobulin G; D012367:RNA, Viral; D018124:Receptors, Tumor Necrosis Factor; D016875:tau Proteins; D016220:Fibroblast Growth Factor 1; D000068800:Etanercept