HIV 感染患者的脑脊髓液淀粉样蛋白和 tau 生物标志物。
Amyloid and tau cerebrospinal fluid biomarkers in HIV infection.
机构信息
Department of Infectious Diseases, University of Gothenburg, Sahlgrenska University Hospital, SE-416 85 Gothenburg, Sweden.
出版信息
BMC Neurol. 2009 Dec 22;9:63. doi: 10.1186/1471-2377-9-63.
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.
背景
由于 HIV 感染和阿尔茨海默病之间不断出现的交集，我们研究了 HIV 感染患者与淀粉样蛋白和 tau 代谢相关的脑脊液（CSF）生物标志物。
方法
在这项横断面研究中，我们测量了 86 例 HIV 感染（HIV+）患者的 CSF 中可溶性淀粉样前体蛋白 alpha 和 beta（sAPPalpha 和 sAPPbeta）、淀粉样蛋白 beta 片段 1-42（Abeta1-42）、总 tau 和磷酸化 tau（t-tau 和 p-tau），包括 21 例艾滋病痴呆综合征（ADC）患者、25 例中枢神经系统（CNS）机会性感染患者和 40 例无神经症状和体征的患者。我们还测量了 64 例未感染（HIV-）患者的这些 CSF 生物标志物，包括 21 例阿尔茨海默病患者，以及年龄较大和较小的无神经疾病对照组。
结果
与其他组相比，ADC 和机会性感染患者的 CSF sAPPalpha 和 sAPPbeta 浓度均升高且降低。与其他 HIV+ 患者相比，机会性感染组而非 ADC 患者的 CSF Abeta1-42 降低。一些 ADC 患者的 CSF t-tau 水平较高，但与 HIV+ 神经无症状组无显著差异，而 HIV+ 各组的 CSF p-tau 均未升高。总之，CSF 淀粉样蛋白和 tau 标志物将 ADC 患者与 HIV+ 和 HIV- 神经无症状患者以及阿尔茨海默病患者区分开来，但不能将其与机会性感染患者区分开来。
结论
ADC 和中枢神经系统机会性感染中 CSF sAPPalpha 和 sAPPbeta 的平行降低提示中枢神经系统免疫激活或炎症对神经元淀粉样前体蛋白合成或加工的影响。一些 ADC 和中枢神经系统感染患者的 CSF t-tau 升高而 p-tau 没有升高，表明存在神经损伤而没有像阿尔茨海默病那样优先积累磷酸化 tau。这些生物标志物的变化定义了 ADC 中脑损伤的发病途径，与阿尔茨海默病不同。
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