Clinical and Research Memory Center, Paris Nord Ile de France Saint Louis Lariboisière Fernand Hospital, AP-HP, University of Paris Diderot, Paris, France.
PLoS One. 2013;8(1):e53587. doi: 10.1371/journal.pone.0053587. Epub 2013 Jan 8.
The cerebrospinal fluid (CSF) levels of the proapoptotic kinase R (PKR) and its phosphorylated PKR (pPKR) are increased in Alzheimer's disease (AD), but whether CSF PKR concentrations are associated with cognitive decline in AD patients remain unknown. In this study, 41 consecutive patients with AD and 11 patients with amnestic mild cognitive impairment (aMCI) from our Memory Clinic were included. A lumbar puncture was performed during the following month of the clinical diagnosis and Mini-Mental State Examination (MMSE) evaluations were repeated every 6 months during a mean follow-up of 2 years. In AD patients, linear mixed models adjusted for age and sex were used to assess the cross-sectional and longitudinal associations between MMSE scores and baseline CSF levels of Aβ peptide (Aβ 1-42), Tau, phosphorylated Tau (p-Tau 181), PKR and pPKR. The mean (SD) MMSE at baseline was 20.5 (6.1) and MMSE scores declined over the follow-up (-0.12 point/month, standard error [SE] = 0.03). A lower MMSE at baseline was associated with lower levels of CSF Aβ 1-42 and p-Tau 181/Tau ratio. pPKR level was associated with longitudinal MMSE changes over the follow-up, higher pPKR levels being related with an exacerbated cognitive deterioration. Other CSF biomarkers were not associated with MMSE changes over time. In aMCI patients, mean CSF biomarker levels were not different in patients who converted to AD from those who did not convert.These results suggest that at the time of AD diagnosis, a higher level of CSF pPKR can predict a faster rate of cognitive decline.
脑脊液（CSF）中促凋亡激酶 R（PKR）及其磷酸化 PKR（pPKR）的水平在阿尔茨海默病（AD）中升高，但 CSF PKR 浓度是否与 AD 患者的认知下降有关尚不清楚。在这项研究中，纳入了来自我们记忆诊所的 41 例连续 AD 患者和 11 例遗忘型轻度认知障碍（aMCI）患者。在临床诊断后的下一个月进行腰椎穿刺，并在平均 2 年的随访期间每 6 个月重复进行 Mini-Mental State Examination（MMSE）评估。在 AD 患者中，使用线性混合模型调整年龄和性别，以评估 MMSE 评分与基线 CSF 中 Aβ肽（Aβ1-42）、Tau、磷酸化 Tau（p-Tau181）、PKR 和 pPKR 之间的横断面和纵向关联。基线时 MMSE 的平均值（SD）为 20.5（6.1），MMSE 评分在随访期间下降（-0.12 分/月，标准误差[SE] = 0.03）。基线时 MMSE 较低与 CSF Aβ1-42 和 p-Tau181/Tau 比值较低有关。pPKR 水平与随访期间纵向 MMSE 变化有关，较高的 pPKR 水平与认知恶化加剧有关。其他 CSF 生物标志物与随时间推移的 MMSE 变化无关。在 aMCI 患者中，从未转为 AD 的患者与转为 AD 的患者相比，CSF 生物标志物水平无差异。这些结果表明，在 AD 诊断时，较高的 CSF pPKR 水平可预测认知下降的更快速度。
