Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

Abstract

BackgroundBecause 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.MethodsIn 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.ResultsCSF 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.ConclusionsParallel 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.

Cognitive impairment and major depressive disorder in HIV infection and cerebrospinal fluid biomarkers

“…faster showing early signs of degenerative diseases usually seen in the elderly makes important the study of aging biomarkers used in the diagnosis of Alzheimer disease in HIV infection 26 .…”

HIV-associated neurocognitive disorders: a changing pattern

“…However, the results regarding tau are discordant between studies: some found an increase of tau in the CSF of patients with HANDs, similar to those with AD [43], whereas others found no increase of CSF tau, either in its total form or its phosphorylated one [44][45][46], thus offering a distinct profile of HAND as compared with AD. Recently, Gisslen et al carried out a comprehensive study of several biomarkers and found that the CSF combination of a low level of soluble APPs (sAPPs)-a and -b and a normal level of phosphorylated tau allowed the discrimination of patients with HAD from both HIV + and HIV -neuroasymptomatics and from AD patients, but not from those future science group HIV + patients with opportunistic infections [47]. They concluded that parallel reductions of CSF sAPP-a and sAPP-b in HAD and opportunistic CNS infections suggest an effect of CNS immune activation or inflammation in neuronal amyloid synthesis or processing [47].…”

Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV in the central nervous system

“…However, they are not clinically applicable 16,17,18,19,20 and are only used in research. With the aging of the HIV population, other biomarkers have become important and have been investigated 21,22,23,24 . The same can be applied to polyneuropathies and myelopathy associated with HIV.…”