Molecular and cellular neurosciences
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The human prion diseases are a diverse set of often rapidly progressive neurodegenerative conditions associated with abnormal forms of the prion protein. We review work to establish diagnostic biomarkers and assays that might fill other important roles, particularly those that could assist the planning and interpretation of clinical trials. The field now benefits from highly sensitive and specific diagnostic biomarkers using cerebrospinal fluid: detecting by-products of rapid neurodegeneration or specific functional properties of abnormal prion protein, with the second generation real time quaking induced conversion (RT-QuIC) assay being particularly promising. ⋯ Blood-based assays have been developed with the potential to screen for variant Creutzfeldt-Jakob disease, although it remains uncertain whether these will ever be used in practice. The very rapid neurodegeneration of prion disease results in strong signals from surrogate protein markers in the blood that reflect neuronal, axonal, synaptic or glial pathology in the brain: notably the tau and neurofilament light chain proteins. We discuss early evidence that such tests, applied alongside robust diagnostic biomarkers, may have potential to add value as clinical trial outcome measures, predictors of future disease course (including for asymptomatic individuals at high risk of prion disease), and as rapidly accessible and sensitive markers to aid early diagnosis.
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Mol. Cell. Neurosci. · Jun 2019
ReviewFluid and PET biomarkers for amyloid pathology in Alzheimer's disease.
Alzheimer's disease (AD) is characterized by amyloid plaques and tau pathology (neurofibrillary tangles and neuropil threads). Amyloid plaques are primarily composed of aggregated and oligomeric β-amyloid (Aβ) peptides ending at position 42 (Aβ42). ⋯ Therefore, sensitive, specific and robust biomarkers to identify brain amyloidosis are central in AD research. Here, we discuss fluid and PET biomarkers for Aβ and their application.
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Mol. Cell. Neurosci. · May 2015
ReviewEpidemiology of mild traumatic brain injury and neurodegenerative disease.
Every year an estimated 42 million people worldwide suffer a mild traumatic brain injury (MTBI) or concussion. More severe traumatic brain injury (TBI) is a well-established risk factor for a variety of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Recently, large epidemiological studies have additionally identified MTBI as a risk factor for dementia. ⋯ The prevalence of CTE is unknown and the amount of MTBI or sub-concussive trauma exposure necessary to produce CTE is unclear. This review will summarize the current literature regarding the epidemiology of MTBI, post-TBI dementia and Parkinson's disease, and CTE while highlighting methodological challenges and critical future directions of research in this field. This article is part of a Special Issue entitled SI:Traumatic Brain Injury.
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Mol. Cell. Neurosci. · May 2015
ReviewNeurological 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. ⋯ 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'.
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Mol. Cell. Neurosci. · May 2015
ReviewNeuroimaging and traumatic brain injury: State of the field and voids in translational knowledge.
Traumatic brain injury (TBI) is a leading cause of death and disability in every developed country in the world and is believed to be a risk factor in the later development of depression, anxiety disorders and neurodegenerative diseases including chronic traumatic encephalopathy (CTE), Alzheimer's Disease (AD), Parkinson's Disease (PD), and amyotrophic lateral sclerosis (ALS). One challenge faced by those who conduct research into TBI is the lack of a verified and validated biomarker that can be used to diagnose TBI or for use as a prognostic variable which can identify those at risk for poor recovery following injury or at risk for neurodegeneration later in life. Neuroimaging continues to hold promise as a TBI biomarker but is limited by a lack of clear relationship between the neuropathology of injury/recovery and the quantitative and image based data that is obtained. ⋯ This review describes the current use and limitations of imaging in TBI including a discussion of currently used animal injury models and the available animal imaging data and extracted markers that hold the greatest promise for helping translate alterations in imaging back to injury pathology. Further, it reviews both the human and animal TBI literature supporting current standards, identifies the remaining voids in the literature, and briefly highlights recent advances in molecular imaging. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.