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Open Access Research article

Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

Magnus Gisslén1*, Jan Krut1, Ulf Andreasson2, Kaj Blennow2, Paola Cinque3, Bruce J Brew4, Serena Spudich5, Lars Hagberg1, Lars Rosengren2, Richard W Price5 and Henrik Zetterberg2

Author Affiliations

1 Department of Infectious Diseases, University of Gothenburg, Sahlgrenska University Hospital, SE-416 85 Gothenburg, Sweden

2 Department of Psychiatry and Neurochemistry, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden

3 Clinic of Infectious Diseases, San Raffaele Hospital, Milan, Italy

4 Departments of Neurology and HIV Medicine, St. Vincent's Hospital, University of New South Wales, Sydney, Australia

5 Department of Neurology, University of California, San Francisco General Hospital, CA, USA

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BMC Neurology 2009, 9:63  doi:10.1186/1471-2377-9-63

Published: 22 December 2009

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.