Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

Magnus Gisslén, Jan Krut, Ulf Andreasson, Kaj Blennow, Paola Cinque, Bruce J. Brew, Serena Spudich, Lars Hagberg, Lars Rosengren, Richard W. Price, Henrik Zetterberg

Research output: Contribution to journalArticle

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 (sAPPα and sAPPβ), amyloid beta fragment 1-42 (Aβ1-42), 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 sAPPα and sAPPβ 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 Aβ1-42 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 sAPPα and sAPPβ 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.

Original languageEnglish
Article number63
JournalBMC Neurology
Volume9
DOIs
Publication statusPublished - Dec 22 2009

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AIDS Dementia Complex
Amyloid
HIV Infections
Cerebrospinal Fluid
Biomarkers
HIV
Opportunistic Infections
Alzheimer Disease
Central Nervous System Infections
Amyloid beta-Protein Precursor
Amyloid beta-Peptides
Brain Injuries
Signs and Symptoms
Central Nervous System
Cross-Sectional Studies
Inflammation

ASJC Scopus subject areas

  • Clinical Neurology

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Gisslén, M., Krut, J., Andreasson, U., Blennow, K., Cinque, P., Brew, B. J., ... Zetterberg, H. (2009). Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. BMC Neurology, 9, [63]. https://doi.org/10.1186/1471-2377-9-63

Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. / Gisslén, Magnus; Krut, Jan; Andreasson, Ulf; Blennow, Kaj; Cinque, Paola; Brew, Bruce J.; Spudich, Serena; Hagberg, Lars; Rosengren, Lars; Price, Richard W.; Zetterberg, Henrik.

In: BMC Neurology, Vol. 9, 63, 22.12.2009.

Research output: Contribution to journalArticle

Gisslén, M, Krut, J, Andreasson, U, Blennow, K, Cinque, P, Brew, BJ, Spudich, S, Hagberg, L, Rosengren, L, Price, RW & Zetterberg, H 2009, 'Amyloid and tau cerebrospinal fluid biomarkers in HIV infection', BMC Neurology, vol. 9, 63. https://doi.org/10.1186/1471-2377-9-63
Gisslén M, Krut J, Andreasson U, Blennow K, Cinque P, Brew BJ et al. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. BMC Neurology. 2009 Dec 22;9. 63. https://doi.org/10.1186/1471-2377-9-63
Gisslén, Magnus ; Krut, Jan ; Andreasson, Ulf ; Blennow, Kaj ; Cinque, Paola ; Brew, Bruce J. ; Spudich, Serena ; Hagberg, Lars ; Rosengren, Lars ; Price, Richard W. ; Zetterberg, Henrik. / Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. In: BMC Neurology. 2009 ; Vol. 9.
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AU - Brew, Bruce J.

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