Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

被引:114
作者
Gisslen, Magnus [1 ]
Krut, Jan [1 ]
Andreasson, Ulf [2 ]
Blennow, Kaj [2 ]
Cinque, Paola [3 ]
Brew, Bruce J. [4 ,5 ]
Spudich, Serena [6 ]
Hagberg, Lars [1 ]
Rosengren, Lars [2 ]
Price, Richard W.
Zetterberg, Henrik [2 ]
机构
[1] Univ Gothenburg, Dept Infect Dis, Sahlgrenska Univ Hosp, SE-41685 Gothenburg, Sweden
[2] Univ Gothenburg, Dept Psychiat & Neurochem, Sahlgrenska Univ Hosp, SE-41685 Gothenburg, Sweden
[3] Hosp San Raffaele, Clin Infect Dis, I-20132 Milan, Italy
[4] Univ New S Wales, St Vincents Hosp, Dept Neurol, Sydney, NSW, Australia
[5] Univ New S Wales, St Vincents Hosp, Dept HIV Med, Sydney, NSW, Australia
[6] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Neurol, San Francisco, CA USA
基金
美国国家卫生研究院; 瑞典研究理事会;
关键词
AIDS DEMENTIA COMPLEX; VIRUS TYPE-1 RNA; ALZHEIMERS-DISEASE; ANTIRETROVIRAL TREATMENT; PRECURSOR PROTEIN; NEUROPATHOLOGIC ASSESSMENT; LEVELS CORRELATE; BACE1; ACTIVITY; VIRAL LOAD; BETA;
D O I
10.1186/1471-2377-9-63
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 (sAPP alpha and sAPP beta), amyloid beta fragment 1-42 (A beta(1-42)), 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 sAPP alpha and sAPP beta 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 A beta(1-42) 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 sAPP alpha and sAPP beta 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.
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页数:13
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