Department of Neurology, Amedeo Avogadro University, Novara, Italy.
J Alzheimers Dis. 2011;27(4):781-90. doi: 10.3233/JAD-2011-111046.
Cerebrospinal fluid (CSF) biomarkers (Aβ₁₋₄₂, total tau, P-181 tau) are currently used to support a clinical diagnosis of Alzheimer's disease (AD). The CSF profile in frontotemporal lobar degeneration (FTLD) caused by Progranulin (GRN) mutation is unknown. We assessed CSF biomarkers in 145 AD, 140 FTLD (20 GRN positive, 120 GRN negative) patients, and 38 controls. Taking into account the reference values used in clinical practice, GRN mutation carriers and controls did not differ significantly for any biomarker, whereas GRN negative FTLD patients had higher tau levels than controls (p < 0.001) and patients carrying GRN Thr272fs mutation (p = 0.033, Chi-Square test). Comparing CSF biomarkers mean values among groups, total tau was significantly increased in GRN negative FTLD and in mutation carriers compared with controls (p < 0.001). P-181 tau CSF was increased in AD patients and in GRN negative FTLD compared with controls (p < 0.001), but not in 17 patients carrying the Thr272fs mutation. 88.2% of mutation carriers had normal CSF tau, despite the neurodegenerative nature of FTLD. Our results suggest that GRN mutation carriers have normal or borderline CSF biomarkers. In patients with an AD-like phenotype but normal or borderline CSF biomarkers, a diagnosis of FTLD-U caused by GRN mutations should be considered.
脑脊液（CSF）生物标志物（Aβ₁₋₄₂、总 tau、P-181 tau）目前用于支持阿尔茨海默病（AD）的临床诊断。由颗粒蛋白前体（GRN）突变引起的额颞叶变性（FTLD）的 CSF 特征尚不清楚。我们评估了 145 例 AD、140 例 FTLD（20 例 GRN 阳性，120 例 GRN 阴性）患者和 38 例对照者的 CSF 生物标志物。考虑到临床实践中使用的参考值，GRN 突变携带者和对照者在任何生物标志物方面均无显著差异，而 GRN 阴性 FTLD 患者的 tau 水平高于对照者（p<0.001）和携带 GRN Thr272fs 突变的患者（p=0.033，卡方检验）。比较各组 CSF 生物标志物的平均值，GRN 阴性 FTLD 和突变携带者的总 tau 明显高于对照者（p<0.001）。与对照者相比，AD 患者和 GRN 阴性 FTLD 患者的 P-181 tau CSF 增加（p<0.001），但携带 Thr272fs 突变的 17 例患者除外。尽管 FTLD 具有神经退行性，但突变携带者中有 88.2%的 CSF tau 正常。我们的研究结果表明，GRN 突变携带者具有正常或临界 CSF 生物标志物。在具有 AD 样表型但 CSF 生物标志物正常或临界的患者中，应考虑诊断为 GRN 突变引起的 FTLD-U。
