Alzheimer Center Rotterdam and Department of Neurology Erasmus Medical Center PO Box 2040, 3000 CA Rotterdam The Netherlands.
Alzheimer's Disease and Other Cognitive Disorders Unit Department of Neurology Hospital Clínic Institut d'Investigació Biomèdica August Pi i Sunyer Villarroel, 170 Barcelona 08036 Spain.
Ann Clin Transl Neurol. 2016 Jul 1;3(8):623-36. doi: 10.1002/acn3.325. eCollection 2016 Aug.
To evaluate cerebrospinal fluid (CSF) and serum neurofilament light chain (NfL) levels in genetic frontotemporal dementia (FTD) as a potential biomarker in the presymptomatic stage and during the conversion into the symptomatic stage. Additionally, to correlate NfL levels to clinical and neuroimaging parameters.
In this multicenter case-control study, we investigated CSF NfL in 174 subjects (48 controls, 40 presymptomatic carriers and 86 patients with microtubule-associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame 72 (C9orf72) mutations), and serum NfL in 118 subjects (39 controls, 44 presymptomatic carriers, 35 patients). In 55 subjects both CSF and serum was determined. In two subjects CSF was available before and after symptom onset (converters). Additionally, NfL levels were correlated with clinical parameters, survival, and regional brain atrophy.
CSF NfL levels in patients (median 6762 pg/mL, interquartile range 3186-9309 pg/mL) were strongly elevated compared with presymptomatic carriers (804 pg/mL, 627-1173 pg/mL, P < 0.001), resulting in a good diagnostic performance to discriminate both groups. Serum NfL correlated highly with CSF NfL (r s = 0.87, P < 0.001) and was similarly elevated in patients. Longitudinal samples in the converters showed a three- to fourfold increase in CSF NfL after disease onset. Additionally, NfL levels in patients correlated with disease severity, brain atrophy, annualized brain atrophy rate and survival.
NfL in both serum and CSF has the potential to serve as a biomarker for clinical disease onset and has a prognostic value in genetic FTD.
评估遗传性额颞叶痴呆（FTD）患者脑脊液（CSF）和血清神经丝轻链（NfL）水平，作为疾病前期和症状转化期的潜在生物标志物，并将其与临床和神经影像学参数相关联。
在这项多中心病例对照研究中，我们共纳入了 174 名研究对象（48 名健康对照者、40 名无症状携带者和 86 名携带微管相关蛋白 tau（MAPT）、颗粒蛋白前体（GRN）和 9 号染色体开放阅读框 72（C9orf72）突变的患者），检测了他们的 CSF NfL 水平，同时还纳入了 118 名研究对象（39 名健康对照者、44 名无症状携带者和 35 名患者），检测了他们的血清 NfL 水平。在 55 名研究对象中，同时检测了 CSF 和血清中的 NfL 水平。在两名患者中，我们在症状出现前后（转化者）获取了 CSF 样本。此外，我们还将 NfL 水平与临床参数、生存和区域性脑萎缩相关联。
与无症状携带者（804pg/ml，627-1173pg/ml，P＜0.001）相比，患者（中位数 6762pg/ml，四分位距 3186-9309pg/ml）的 CSF NfL 水平明显升高，这使我们能够很好地鉴别两组患者。血清 NfL 与 CSF NfL 高度相关（r s = 0.87，P＜0.001），患者的血清 NfL 水平也同样升高。在转化者的纵向样本中，我们发现 CSF NfL 在疾病发病后 3-4 倍增加。此外，患者的 NfL 水平与疾病严重程度、脑萎缩、年脑萎缩率和生存相关。
血清和 CSF 中的 NfL 均具有作为遗传性 FTD 临床疾病发病的生物标志物的潜力，并具有预后价值。
