Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Osborn, Katie E.; Khan, Omair A.; Kresge, Hailey A.; Bown, Corey W.; Liu, Dandan; Moore, Elizabeth E.; Gifford, Katherine A.; Acosta, Lealani Mae Y.; Bell, Susan P.; Hohman, Timothy J.; Blennow, Kaj; Zetterberg, Henrik; Jefferson, Angela L.

doi:10.1016/j.dadm.2019.08.008

Cited by 48 publications

(67 citation statements)

References 32 publications

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“…On the assumption that elevated NFL reflects white‐matter insult, the absence of an NFL‐cognition relation is in line with demonstrations of weak and non‐significant associations between white matter and cognitive decline in aging 11,21 . Some studies have found that high NFL levels relate to poor cognition, 6,28,29 but observations of stronger correlations of cognition to NFL in individuals with MCI and AD than in controls suggest that a common disease factor could have influenced some previous observations of NFL–cognition relations.…”

Section: Discussionsupporting

confidence: 76%

Elevated plasma neurofilament light in aging reflects brain white‐matter alterations but does not predict cognitive decline or Alzheimer's disease

Nyberg

Lundquist

Adolfsson

et al. 2020

Alzheimer's & Dementia: Diagnosis, Assessment &

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Introduction We investigated neurofilament light (NFL) accumulation in normal aging as well as in preclinical and clinical Alzheimer's disease (AD) and assessed individual differences in NFL load in relation to cognition and brain white‐matter integrity. Methods We analyzed longitudinal data covering 30 years (1988–2017). Cognitive testing was done up to six times. Plasma NFL was quantified for controls and 142 cases who developed AD over time, and longitudinal changes in NFL were quantified for 100 individuals with three brain‐imaging sessions. Results Longitudinal analyses revealed age‐related NFL increases with marked variability. AD cases had elevated NFL levels, while no significant group differences were seen in the preclinical phase. Variability in NFL levels showed non‐significant correlations with cognition but was associated with brain white matter. Discussion Our findings suggest that elevated blood NFL, likely reflecting brain white‐matter alterations, characterizes clinical AD, while NFL levels do not predict age‐related cognitive impairment or impending AD.

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Section: Discussionsupporting

confidence: 76%

Elevated plasma neurofilament light in aging reflects brain white‐matter alterations but does not predict cognitive decline or Alzheimer's disease

Nyberg

Lundquist

Adolfsson

et al. 2020

Alzheimer's & Dementia: Diagnosis, Assessment &

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“…Emerging evidence indicates that NfL is involved in the pathological mechanism of cognitive declines [ 29 ]. A Chinese Taipei study showed that plasma NfL is a biomarker of cognitive decline in AD and Parkinson's disease (PD), and it is more specific for AD [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of Serum Neurofilament Light Chain Associated with Cognitive Impairment in Vascular Dementia

Zhang

et al. 2020

Disease Markers

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Objective. Vascular dementia (VaD) is a progressive neurodegenerative disease with cognitive decline caused by cerebrovascular factors. Despite the great progress made in the past decade, VaD still lacks effective treatments and peripheral blood biomarkers. In this study, we tested the level of peripheral blood neurofilament light chain (NfL) in VaD patients and explored its relationship with cognitive impairment. Method. A total of 176 study subjects including 80 normal controls (NC) and 96 VaD patients were included in our study. Upon admission, we collected clinical and biochemical characteristics of all research subjects. We also evaluate the Montreal cognitive assessment scale (MoCA) scores of all subjects. The serum NfL level was measured by the single-molecule array (Simoa) method. Results. The years of education in the NC group and VaD group were ( 11.65 ± 3.04 ) years and ( 10.53 ± 3.87 ) years, respectively. Compared with VaD patients, the NC group has a higher level of education ( p = 0.037 ). Furthermore, the results of Simoa indicated that VaD subjects had higher serum NfL levels compared with the NC group [( 8.49 ± 2.37 ) pg/ml vs. ( 19.26 ± 4.71 ) pg/ml, p < 0.001 ]. In terms of other clinical and biochemical characteristics, there was no significant difference between VaD and NC. The Spearman correlation analysis indicated that educational years have a significant positive correlation with MoCA scores ( r = 0.238 , p = 0.041 ), while age and serum NfL levels have a significantly negative correlation with MoCA scores (age: r = − 0.213 , p = 0.040 ; NfL: r = − 0.395 , p = 0.027 ). However, further multiple regression analysis showed that only serum NfL level might serve as an independent risk factor for cognitive decline in VaD ( β = 0.317 , p = 0.021 ). Conclusion. The serum NfL levels in VaD subjects are significantly elevated, which may be used as a potential peripheral blood marker for predicting cognitive impairment in patients with VaD.

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“…Therefore, it represents a non-specific marker for neuronal damage and has been largely studied in the context of neurodegenerative diseases, including multiple sclerosis (MS), Parkinson’s disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) [ 14 ]. Elevated levels of CSF NfL were found in patients with MCI and AD, associating with the severity of memory impairment as a marker of disease progression [ 15 , 16 , 17 ]. Altogether, studies reported a very good performance of CSF NfL to distinguish AD cases from cognitively healthy controls with no evidence of structural brain damage [ 18 ].…”

Section: Emerging Ad Biomarkers In Biological Fluidsmentioning

confidence: 99%

Molecular and Imaging Biomarkers in Alzheimer’s Disease: A Focus on Recent Insights

Clara

Lavitrano

Salvatore

et al. 2020

JPM

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Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly, affecting millions of people worldwide and clinically characterized by a progressive and irreversible cognitive decline. The rapid increase in the incidence of AD highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods rely on measures of amyloid-β (Aβ), phosphorylated (p-tau) and total tau (t-tau) protein levels in the cerebrospinal fluid (CSF) aided by advanced neuroimaging techniques like positron emission tomography (PET) and magnetic resonance imaging (MRI). However, the invasiveness of these procedures and the high cost restrict their utilization. Hence, biomarkers from biological fluids obtained using non-invasive methods and novel neuroimaging approaches provide an attractive alternative for the early diagnosis of AD. Such biomarkers may also be helpful for better understanding of the molecular mechanisms underlying the disease, allowing differential diagnosis or at least prolonging the pre-symptomatic stage in patients suffering from AD. Herein, we discuss the advantages and limits of the conventional biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.

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Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Cited by 48 publications

References 32 publications

Elevated plasma neurofilament light in aging reflects brain white‐matter alterations but does not predict cognitive decline or Alzheimer's disease

Elevated plasma neurofilament light in aging reflects brain white‐matter alterations but does not predict cognitive decline or Alzheimer's disease

Elevated Levels of Serum Neurofilament Light Chain Associated with Cognitive Impairment in Vascular Dementia

Molecular and Imaging Biomarkers in Alzheimer’s Disease: A Focus on Recent Insights

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