Department of Neurology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Department of Neurology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Neurobiol Dis. 2022 May;166:105662. doi: 10.1016/j.nbd.2022.105662. Epub 2022 Feb 12.
Cerebrospinal fluid (CSF) neurofilament light chain (NfL) reflects neuro-axonal damage and is increasingly used to evaluate disease progression across neurological conditions including Alzheimer disease (AD). However, it is unknown how NfL relates to specific types of brain tissue. We sought to determine whether CSF NfL is more strongly associated with total gray matter, white matter, or white matter hyperintensity (WMH) volume, and to quantify the relative importance of brain tissue volume, age, and AD marker status (i.e., APOE genotype, brain amyloidosis, tauopathy, and cognitive status) in predicting CSF NfL.
419 participants (Clinical Dementia Rating [CDR] Scale > 0, N = 71) had CSF, magnetic resonance imaging (MRI), and neuropsychological data. A subset had amyloid positron emission tomography (PET) and tau PET. Pearson correlation analysis was used to determine the association between CSF NfL and age. Multiple regression was used to determine which brain volume (i.e., gray, white, or WMH volume) most strongly associated with CSF NfL. Stepwise regression and dominance analyses were used to determine the individual contributions and relative importance of brain volume, age, and AD marker status in predicting CSF NfL.
CSF NfL increased with age (r = 0.59, p < 0.001). Elevated CSF NfL was associated with greater total WMH volume (p < 0.001), but not gray or white matter volume (p's > 0.05) when considered simultaneously. Age and WMH volume were consistently more important (i.e., have greater R values) than AD markers when predicting CSF NfL.
CSF NfL is a non-specific marker of aging and white matter integrity with limited sensitivity to specific markers of AD. CSF NfL likely reflects processes associated with cerebrovascular disease.
脑脊液（CSF）神经丝轻链（NfL）反映神经轴突损伤，越来越多地用于评估包括阿尔茨海默病（AD）在内的各种神经疾病的疾病进展。然而，目前尚不清楚 NfL 与特定类型的脑组织之间的关系。我们旨在确定 CSF NfL 是否与总灰质、白质或白质高信号（WMH）体积的相关性更强，并定量分析脑体积、年龄和 AD 标志物状态（即 APOE 基因型、脑淀粉样变性、tau 病和认知状态）在预测 CSF NfL 中的相对重要性。
419 名参与者（临床痴呆评定量表[CDR]评分>0，N=71）接受了 CSF、磁共振成像（MRI）和神经心理学数据检测。部分参与者接受了淀粉样蛋白正电子发射断层扫描（PET）和 tau PET 检测。采用 Pearson 相关分析确定 CSF NfL 与年龄之间的相关性。采用多元回归分析确定与 CSF NfL 相关性最强的脑容量（即灰质、白质或 WMH 体积）。采用逐步回归和优势分析确定脑体积、年龄和 AD 标志物状态在预测 CSF NfL 中的个体贡献和相对重要性。
CSF NfL 随年龄增加而升高（r=0.59，p<0.001）。当同时考虑时，CSF NfL 升高与总 WMH 体积增加相关（p<0.001），但与灰质或白质体积无关（p>0.05）。在预测 CSF NfL 时，年龄和 WMH 体积始终比 AD 标志物更重要（即 R 值更高）。
CSF NfL 是衰老和白质完整性的非特异性标志物，对 AD 的特异性标志物敏感性有限。CSF NfL 可能反映与脑血管疾病相关的过程。
