Cerebrospinal fluid (CSF) neurofilament light (NfL) concentration has reproducibly been shown to reflect neurodegeneration in brain disorders, including Alzheimer’s disease (AD). NfL concentration in blood correlates with the corresponding CSF levels, but few studies have directly compared the reliability of these 2 markers in sporadic AD. Herein, we measured plasma and CSF concentrations of NfL in 478 cognitively unimpaired (CU) subjects, 227 patients with mild cognitive impairment, and 113 patients with AD dementia. We found that the concentration of NfL in CSF, but not in plasma, was increased in response to Aβ pathology in CU subjects. Both CSF and plasma NfL concentrations were increased in patients with mild cognitive impairment and AD dementia. Furthermore, only NfL in CSF was associated with reduced white matter microstructure in CU subjects. Finally, in a transgenic mouse model of AD, CSF NfL increased before serum NfL in response to the development of Aβ pathology. In conclusion, NfL in CSF may be a more reliable biomarker of neurodegeneration than NfL in blood in preclinical sporadic AD.

中文翻译：

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血液和脑脊液神经丝光差异检测早期阿尔茨海默病的神经变性

脑脊液 (CSF) 神经丝光 (NfL) 浓度已被重复显示可反映脑部疾病（包括阿尔茨海默病 (AD)）的神经退行性变。血液中的 NfL 浓度与相应的 CSF 水平相关，但很少有研究直接比较这两种标志物在散发性 AD 中的可靠性。在此，我们测量了 478 名认知未受损 (CU) 受试者、227 名轻度认知障碍患者和 113 名 AD 痴呆患者的血浆和脑脊液 NfL 浓度。我们发现 CSF 中 NfL 的浓度（而非血浆中）随着 CU 受试者的 Aβ 病理学而增加。轻度认知障碍和 AD 痴呆患者的脑脊液和血浆 NfL 浓度均增加。此外，只有脑脊液中的 NfL 与 CU 受试者的白质微观结构减少有关。最后，在 AD 的转基因小鼠模型中，CSF NfL 在血清 NfL 之前增加，以响应 Aβ 病理的发展。总之，在临床前散发性 AD 中，CSF 中的 NfL 可能是比血液中的 NfL 更可靠的神经变性生物标志物。