P1‐247: Cerebrospinal Fluid Neurofilament Light Protein as a Differential Diagnosis Biomarker in Neurological Diseases: A Systematic Review and Metaanalysis

Bridel, Claire; Wieringen, Wessel N. van; Zettenberg, Henrik; Visser, Pieter Jelle; Tijms, Betty M.; Teunissen, Charlotte E.

doi:10.1016/j.jalz.2018.06.252

Cited by 20 publications

(37 citation statements)

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“…The biomarker can be measured in both CSF and plasma (or serum), and virtually all CSF findings have been replicated in blood with sensitive assays [69]. The highest NfL levels are seen in frontotemporal, vascular and HIV-associated dementias [70]. However, the findings in familial AD are also very clear; mutation carriers show a sudden change in their blood NfL levels around a decade before expected clinical onset, which probably marks the onset of neurodegeneration, and the higher the increase, the more rapid clinical disease progression [71,72].…”

Section: Biomarkers For Neurodegenerationmentioning

confidence: 99%

Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies

2020

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Clinical trial results presented in 2019 suggest that antibody-based removal of cerebral amyloid β (Aβ) plaques may possibly clear tau tangles and modestly slow cognitive decline in symptomatic Alzheimer's disease (AD). Although regulatory approval of this approach is still pending, preparing the healthcare system for the advent of disease-modifying therapies against AD is imperative. In particular, it will be necessary to identify the most suitable biomarkers to facilitate appropriate treatment of AD. Here, we give an update on recent developments in fluid and imaging biomarkers for AD-related pathologies and discuss potential approaches which could be adopted to screen for and clarify the underlying pathology in people seeking medical advice because of cognitive symptoms. We succinctly review recent data regarding biomarkers for Aβ and tau pathology, neurodegeneration, synaptic dysfunction and inflammation, highlight the need for further research into common co-pathologies, and suggest how different biomarkers could be used (most likely in combination) to facilitate the development and clinical implementation of novel drug candidates against AD.

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Section: Biomarkers For Neurodegenerationmentioning

confidence: 99%

Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies

2020

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“…NfL, a now widely validated marker of neurodegeneration [16], was relatively low in early life, but in both controls and DS, NfL increased steadily after age 30. Importantly, NfL levels in plasma of individuals with DS started to diverge from control levels in the 31-40 years age group and were most different in the two oldest age groups.…”

Section: Discussionmentioning

confidence: 97%

“…Now with the advent of reliable methods it is possible to assess whether tau and neurofilament light (NfL) are also altered in DS. NfL, a scaffolding cytoskeleton protein, is elevated in plasma in many neurodegenerative conditions [16], and several NfL assays are available [17]. Measurement of tau in plasma has been less straightforward.…”

mentioning

confidence: 99%

Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ42 decrease with age, whereas NT1 tau and NfL increase

Mengel

Glynn

et al. 2020

Preprint

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Background Down syndrome (DS) is the most common genetic cause of Alzheimer’s Disease (AD), but diagnosis of AD in DS is challenging due to the intellectual disability which accompanies DS. When disease-modifying agents for AD are approved, reliable biomarkers will be required to identify when and how long people with DS should undergo treatment. Three cardinal neuropathological features characterize AD, and AD in DS – Aβ amyloid plaques, tau neurofibrillary tangles, and neuronal loss. Here, we quantified plasma biomarkers of all 3 neuropathological features in a large cohort of people with DS aged from 3 months to 68 years. Methods Using ultra-sensitive single molecule array (Simoa) assays, we measured 3 analytes (Aβ42, NfL, and tau) in plasmas of 100 individuals with DS and 100 age- and sex-matched controls. Tau was measured using an assay (NT1) which detects forms of tau containing at least residues 6-198, and the stability of the 3 analytes was established using plasma from ten healthy volunteers collected at 6 intervals over a five day period. Results High Aβ42 and NT1 tau, and low NfL, were observed in infants. Across all ages, Aβ42 levels were higher in DS than controls. Levels of Aβ42 decreased with age in both DS and controls, but this decrease was greater in DS than controls and became prominent in the third decade of life. NT1 tau fell in adolescents and young adults, but increased in older individuals with DS. NfL levels were low in infants, children, adolescents and young adults, but thereafter increased in DS compared to controls. Conclusions High levels of Aβ42 and tau in both young controls and DS suggest these proteins are produced by normal physiological processes, whereas, the changes seen in later life are consistent with emergence of pathological alterations. Our plasma biomarker results are in good agreement with prior neuropathology studies and indicate that the third and fourth decades (i.e. 20 to 40 years of age) of life are pivotal periods during which AD processes manifest in DS. Application of the assays used here to longitudinal studies of individuals with DS aged 20 to 50 years of age, should further validate the use of these biomarkers, and in time may allow identification and monitoring of people with DS best suited for treatment with emerging AD therapies.

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“…CSF biomarkers continue to be investigated for potential diagnosis of various neurological conditions including different forms of neurodegeneration [110][111][112][113]. In Alzheimer's disease (AD), many studies have focused on increases in CSF Aβ or tau species, proteins that are harmful, or injury markers such as neurofilament light chain.…”

Section: Csf Biomarkersmentioning

confidence: 99%

This was the year that was: brain barriers and brain fluid research in 2019

Keep

Jones²,

Drewes

2020

Fluids Barriers CNS

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This editorial highlights advances in brain barrier and brain fluid research published in 2019, as well as addressing current controversies and pressing needs. Topics include recent advances related to: the cerebral endothelium and the neurovascular unit; the choroid plexus, arachnoid membrane; cerebrospinal fluid and the glymphatic hypothesis; the impact of disease states on brain barriers and brain fluids; drug delivery to the brain; and translation of preclinical data to the clinic. This editorial also mourns the loss of two important figures in the field, Malcolm B. Segal and Edward G. Stopa.

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P1‐247: Cerebrospinal Fluid Neurofilament Light Protein as a Differential Diagnosis Biomarker in Neurological Diseases: A Systematic Review and Metaanalysis

Cited by 20 publications

References 0 publications

Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies

Biomarkers for Alzheimer’s disease—preparing for a new era of disease-modifying therapies

Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ42 decrease with age, whereas NT1 tau and NfL increase

This was the year that was: brain barriers and brain fluid research in 2019

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