Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease

Initiative, Alzheimer’s Disease Neuroimaging

doi:10.1001/jamaneurol.2016.6117

Cited by 751 publications

(938 citation statements)

References 32 publications

Supporting

112

Mentioning

749

Contrasting

Unclassified

Order By: Relevance

“…Another study found that a panel of serum proteins has diagnostic value 161 , although the sensitivity and specificity of this test need improvement. Individual blood proteins, including biomarkers of neurodegeneration (such as neurofilament light protein, neuron-specific enolase and heart fatty acid binding protein) and glial activation biomarkers (such as YKL-40 and monocyte chemotactic protein 1) also exhibit potential for AD diagnosis and prognostication [162][163][164][165] . Leukocyte surface protein phenotyping and functional phenotyping might also prove useful; leukocyte surface expression of P2X7 is decreased in patients with AD and is linked to altered phagocytic function of monocytes 45 .…”

Section: Blood Proteinsmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

View full text Add to dashboard Cite

The global burden of Alzheimer disease (AD), already the most common type of dementia, is expected to increase still further owing to population ageing. AD not only causes severe distress for patients and caregivers, but also results in a large economic burden on society. Current major challenges in AD include the lack of reliable biomarkers for its early diagnosis, as well as the lack of effective preventive strategies and treatments 1,2 . Thus, increased understanding of the molecular patho genesis of AD could lead to the development of improved diagnostic and therapeutic strategies.AD is conventionally regarded as a CNS disorder. However, increasing experimental, epidemiological and clinical evidence has suggested that manifestations of AD extend beyond the brain. These systemic alterations might not be simply secondary effects of the cerebral degeneration seen in AD, but could reflect under lying processes linked to progression of the disease. AD pathogenesis is complex, involving abnormal amyloid-β (Aβ) metabolism, tau hyperphosphorylation, oxidative stress, reactive glial and microglial changes, and other pathological events. Given that Aβ is a major hallmark of AD and a fertile area of research in this disease, this Review focuses on the systemic role of Aβ in AD. We discuss the communication between peripheral and central pools of Aβ, and describe interactions between systemic abnormalities and AD pathogenesis in the brain. We review emerging findings of associations between systemic abnormalities and Aβ metabolism, and describe how these associations might interact with or reflect on the central pathways of Aβ production and clearance. On the basis of these findings, we suggest that interactions between the brain and the periphery might have a crucial role in the development and progression of AD. Aβ biogenesis and catabolismA steady accrual of data from laboratories and clinics is providing increasing support for the concept that an imbalance between the production and clearance of Aβ is a very early (and often initiating) factor in AD 3 . Normal metabolism of Aβ and maintenance of the homeostatic balance between Aβ production and clearance is, therefore, essential to maintain brain health. In fact, physiological metabolism of Aβ occurs not only in the brain but also in the periphery, and communication between these regions is possible (FIG. 1). Central and peripheral production of AβAβ is derived from the proteolytic cleavage of amyloid precursor protein (APP), which is expressed not only in brain cells, including neurons, astrocytes and microglia, but also in peripheral organs and tissues, such as the Abstract | Alzheimer disease (AD) is the most common type of dementia, and is currently incurable; existing treatments for AD produce only a modest amelioration of symptoms. Research into this disease has conventionally focused on the CNS. However, several peripheral and systemic abnormalities are now understood to be linked to AD, and our understanding of how these alterations contribute to AD is becom...

show abstract

Section: Blood Proteinsmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The most recent studies using single molecule array (Simoa) technique for NFL determination have shown significantly higher serum NFL levels in the AD group even in prodromal stadium compared to normal controls. However the overlap between the AD and other diagnostic groups was obvious 14,15 . Despite this limitation plasma NFL levels may be a useful noninvasive biomarker of neurodegenerative processes 15 .…”

Section: Discussionmentioning

confidence: 99%

“…However the overlap between the AD and other diagnostic groups was obvious 14,15 . Despite this limitation plasma NFL levels may be a useful noninvasive biomarker of neurodegenerative processes 15 . Considering the different functions of individual NF chains and that variations in NF stoichiometry are assumed to be involved in the process of neurodegeneration 49 , we were interested whether the NFL/NFH ratio has any diagnostic potential.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neurofilaments and tau proteins in cerebrospinal fluid and serum in dementias and neuroinflammation

Fialová¹,

Bartoš²,

Švarcová³

2017

BIOMED PAP

View full text Add to dashboard Cite

Aims. The aim of this study was to evaluate the diagnostic potential of cerebrospinal fluid (CSF) and serum levels of neurocytoskeletal proteins and their ratios for the diagnosis of dementias and to assess the differences in neurocytoskeletal proteins between neurodegeneration and neuroinflammation. Methods. CSF and serum levels of neurofilament light subunits (NFL) and neurofilament heavy subunits (NFH) as well as CSF levels of total tau (t-tau) and phosphorylated tau (p-tau) proteins were determined using ELISA in 20 Alzheimer's disease patients (AD group), 13 patients with other dementias (OD group), 17 patients with inflammatory aseptic neuro-infections (IP), and 20 aged-matched cognitively normal elderly persons (NC group). Results. The ratio CSF p-tau/t-tau was significantly higher in the NC group than that in the AD or OD groups (P<0.0005 for each group). The CSF NFH/p-tau and CSF NFL/p-tau ratios were significantly lower in AD patients than OD patients (P≤0.003). Serum and CSF NFL and CSF NFH levels were significantly higher in OD patients than AD patients (P≤0.03).The lowest values of the CSF NFL/NFH ratio were found in the IP group and they significantly differed from those in normal controls (P<0.0001) and any dementia group (IP vs. AD P<0.0001; IP vs. OD P=0.03). Conclusion. CSF tau proteins and their index differentiated between AD or OD patients and cognitively normal subjects, while CSF levels of neurofilaments expressed as their index seem to contribute to the discrimination between patients with neuroinflammation and normal controls or AD patients.

show abstract

“…The NfL increases in manifest Huntington's disease were similar to those in multiple sclerosis relapses, 5 and were at least as great as in other neurodegenerative diseases including progressive supranuclear palsy, 6 multiple system atrophy, 7 and corticobasal syndrome. In Parkinson's disease 7 and Alzheimer's disease, 8 plasma and blood NfL concentrations are not substantially different from those of controls, partly because of the wide range of disease severity and subtypes within those diseases. In Huntington's disease, since patients can be genetically tested and subgrouped by time to expected motor onset, NfL concentrations have the potential to be used to study disease biology directly.…”

mentioning

confidence: 93%

Potential biomarker breakthrough for Huntington's disease

Ross

Bang

2017

The Lancet Neurology

View full text Add to dashboard Cite

Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease

Cited by 751 publications

References 32 publications

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

Neurofilaments and tau proteins in cerebrospinal fluid and serum in dementias and neuroinflammation

Potential biomarker breakthrough for Huntington's disease

Contact Info

Product

Resources

About