Introduction: The potential of neurofilament light (NfL) as a blood-based biomarker is currently being investigated in autosomal dominant neurodegenerative disease. This study explores the clinical utility of serum-NfL in frontotemporal dementia due to CHMP2B mutation (FTD-3). Methods: This cross-sectional study included serum and CSF data from 38 members of the Danish FTD-3 family: 12 affected CHMP2B mutation carriers, 10 presymptomatic carriers, and 16 noncarriers. Serum-NfL levels measured by single-molecule array (Simoa) technology were tested for associations with the clinical groups and clinical parameters. Serum and CSF data were compared, and CSF/serum-albumin ratio was included as a measure of blood-brain barrier (BBB) function. Results: Serum-NfL concentrations were significantly increased in symptomatic CHMP2B mutation carriers compared to presymptomatic carriers and in both groups compared to healthy family controls. Serum-NfL levels appear to increase progressively with age in presymptomatic carriers, and this is perhaps followed by a change in trajectory when patients become symptomatic. Measurements of NfL in serum and CSF were highly correlated and fold-changes in serum and CSF between clinical groups were similar. Increase in serum-NFL levels was correlated with reduced ACE-score. Higher CSF/serum-albumin ratios were demonstrated in FTD-3 patients, but this did not affect the significant associations between serum-NfL and clinical groups. Conclusion: Serum-NfL could be utilized as an accurate surrogate marker of CSF levels to segregate symptomatic CHMP2B carriers, presymptomatic carriers, and non-carriers. The observed indication of BBB dysfunction in FTD-3 patients did not confound this use of serum-NfL. The results support the occurrence of mutation-related differences in NfL dynamics in familial FTD.
Dement Geriatr Cogn Disord

中文翻译：

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CHMP2B突变致额颞叶痴呆患者血清神经丝光

简介：目前正在研究神经丝光 (NfL) 作为基于血液的生物标志物在常染色体显性神经退行性疾病中的潜力。本研究探讨了血清 NfL 在CHMP2B突变（FTD-3）引起的额颞叶痴呆中的临床效用。方法：这项横断面研究包括来自丹麦 FTD-3 家族 38 名成员的血清和脑脊液数据：12 名受影响的CHMP2B突变携带者、10 名症状前携带者和 16 名非携带者。测试通过单分子阵列 (Simoa) 技术测量的血清 NfL 水平与临床组和临床参数的关联。比较血清和脑脊液数据，并包括脑脊液/血清白蛋白比率作为血脑屏障 (BBB) 功能的衡量标准。结果：与症状前携带者相比，有症状的CHMP2B突变携带者以及与健康家庭对照相比，两组的血清 NfL 浓度均显着增加。无症状携带者的血清 NfL 水平似乎随着年龄的增长而逐渐增加，并且当患者出现症状时，可能随后轨迹发生变化。血清和脑脊液中 NfL 的测量值高度相关，临床组之间血清和脑脊液的倍数变化相似。血清 NFL 水平的增加与 ACE 评分的降低相关。FTD-3 患者的脑脊液/血清白蛋白比率较高，但这并不影响血清 NfL 与临床组之间的显着关联。结论：血清 NfL 可用作 CSF 水平的准确替代标志物，以区分有症状的CHMP2B携带者、症状前携带者和非携带者。在 FTD-3 患者中观察到的 BBB 功能障碍迹象并未混淆血清 NfL 的这种使用。结果支持在家族性 FTD 中 NfL 动力学中发生与突变相关的差异。
老年痴呆症认知障碍