Neurological consequences of traumatic brain injuries in sports.

Traumatic brain injury (TBI) is common in boxing and other contact sports. The long term irreversible and progressive aftermath of TBI in boxers depicted as punch drunk syndrome was described almost a century ago and is now widely referred as chronic traumatic encephalopathy (CTE). The short term sequelae of acute brain injury including subdural haematoma and catastrophic brain injury may lead to death, whereas mild TBI, or concussion, causes functional disturbance and axonal injury rather than gross structural brain damage. Following concussion, symptoms such as dizziness, nausea, reduced attention, amnesia and headache tend to develop acutely but usually resolve within a week or two. Severe concussion can also lead to loss of consciousness. Despite the transient nature of the clinical symptoms, functional neuroimaging, electrophysiological, neuropsychological and neurochemical assessments indicate that the disturbance of concussion takes over a month to return to baseline and neuropathological evaluation shows that concussion-induced axonopathy may persist for years. The developing brains in children and adolescents are more susceptible to concussion than adult brain. The mechanism by which acute TBI may lead to the neurodegenerative process of CTE associated with tau hyperphosphorylation and the development of neurofibrillary tangles (NFTs) remains speculative. Focal tau-positive NFTs and neurites in close proximity to focal axonal injury and foci of microhaemorrhage and the predilection of CTE-tau pathology for perivascular and subcortical regions suggest that acute TBI-related axonal injury, loss of microvascular integrity, breach of the blood brain barrier, resulting inflammatory cascade and microglia and astrocyte activation are likely to be the basis of the mechanistic link of TBI and CTE. This article provides an overview of the acute and long-term neurological consequences of TBI in sports. Clinical, neuropathological and the possible pathophysiological mechanisms are discussed. This article is part of a Special Issue entitled 'Traumatic Brain Injury'

Plasma neurofilament light in progressive multiple sclerosis

Neurofilaments (Nfs) are a family of neuronal intermediate filaments involved in the growth and stability of axons, and, through incorporation into different supramolecular assemblies, also in synaptic organization and function in the central nervous system. Pioneering work by Lars Rosengren and colleagues in the late 1980s led to the establishment of an enzyme‐linked immunosorbent assay (ELISA) based on polyclonal antisera that allowed for the reliable quantification of the neurofilament light (NfL) subunit in cerebrospinal fluid (CSF)

Neurochemical markers of traumatic brain injury – relevance to acute diagnostics, disease monitoring, and neuropsychiatric outcome prediction

Considerable advancements have been made in the quantification of biofluid-based biomarkers for traumatic brain injury (TBI), which provide a clinically accessible window to investigate disease mechanisms and progression. Methods with improved analytical sensitivity compared with standard immunoassays are increasingly utilized, which has opened for the use of blood tests in the diagnosis, monitoring, and outcome prediction of TBI. Most work to date has focused on acute TBI diagnostics, whilst the literature on biomarkers for long-term sequelae is relatively scarce. In this review, we give an update on the latest developments in biofluid-based biomarker research in TBI and discuss how acute and prolonged biomarker changes can be used to detect and quantify brain injury and predict clinical outcome and neuropsychiatric sequelae

The phosphorylation cascade hypothesis of Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ)-induced phosphorylation of the axon-stabilizing tau protein, which causes neurodegeneration. Here, Morshed et al. show that deregulated phosphorylation in AD also affects other proteins and cell types in the brain, suggesting that the tau-centric view on Aβ toxicity should be revised

In the blood: biomarkers for amyloid pathology and neurodegeneration in Alzheimer's disease

This scientific commentary refers to 'Plasma total-tau, neurofilament light chain and amyloid-β levels and risk of dementia: a population-based study' by de Wolf et al. (https://doi.org/10.1093/brain/awaa054), and 'Relationship of amyloid-b1-42 in blood and brain amyloid: Ginkgo Evaluation of Memory Study' by Lopez et al. (https://doi.org/10.1093/braincomms/fcz038), two papers that illustrate these latest developments

Moving fluid biomarkers for Alzheimer's disease from research tools to routine clinical diagnostics

Four fluid-based biomarkers have been developed into diagnostic tests for Alzheimer’s disease (AD) pathology: the ratio of 42 to 40 amino acid-long amyloid β, a marker of plaque pathology; total-tau and phosphorylated tau, markers of AD-related changes in tau metabolism and secretion; and neurofilament light, a marker of neurodegeneration. When measured in cerebrospinal fluid, these biomarkers can be used in clinical practice to support a diagnosis of mild cognitive impairment or dementia due to AD. Recently, technological breakthroughs have made it possible to measure them in standard blood samples as well. Here, we give an updated account of the current state of the fluid-based AD biomarker research field. We discuss how the new blood tests may be used in research and clinical practice, and what role they may play in relation to more established diagnostic tests, such as CSF biomarkers and amyloid and tau positron emission tomography, to facilitate the effective implementation of future disease-modifying therapies