title: Amyloid and tau cerebrospinal fluid biomarkers in HIV infection.
abstract: BACKGROUND
  Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients.
  
  
  METHODS
  In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPalpha and sAPPbeta), amyloid beta fragment 1-42 (Abeta1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease.
  
  
  RESULTS
  CSF sAPPalpha and sAPPbeta concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Abeta1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections.
  
  
  CONCLUSIONS
  Parallel reductions of CSF sAPPalpha and sAPPbeta in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.
authors.affiliation: Department of Infectious Diseases, University of Gothenburg, Sahlgrenska University Hospital, SE-416 85 Gothenburg, Sweden. magnus.gisslen@infect.gu.se
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslén
authors.forename: Jan
authors.initials: J
authors.lastname: Krut
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Paola
authors.initials: P
authors.lastname: Cinque
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
authors.forename: Serena
authors.initials: S
authors.lastname: Spudich
authors.forename: Lars
authors.initials: L
authors.lastname: Hagberg
authors.forename: Lars
authors.initials: L
authors.lastname: Rosengren
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid; D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000134:cerebrospinal fluid; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000097:blood / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid*; D025341:Principal Component Analysis; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins