Frontiers in neurology
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Tau misfolding and aggregation leads to the formation of neurofibrillary tangles (NFTs), which have long been considered one of the main pathological hallmarks for numerous neurodegenerative diseases known as tauopathies, including Alzheimer's Disease (AD) and Parkinson's Disease (PD). However, recent studies completed both in vitro and in vivo suggest that intermediate forms of tau, known as tau oligomers, between the monomeric form and NFTs are the true toxic species in disease and the best targets for anti-tau therapies. However, the exact mechanism by which the spread of pathology occurs is unknown. ⋯ Recently, researchers have reported the ability of tau oligomers to enter and exit cells, propagating from disease-affected regions to unaffected areas. While the mechanism by which the spreading of misfolded tau occurs has yet to be elucidated, there are a few different models which have been proposed, including cell membrane stress and pore-formation, endocytosis and exocytosis, and non-traditional secretion of protein not enclosed by a membrane. Coming to an understanding of how toxic tau species seed and spread through the brain will be crucial to finding effective treatments for neurodegenerative tauopathies.
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Frontiers in neurology · Jan 2013
Stroke prevention and cognitive reserve: emerging approaches to modifying risk and delaying onset of dementia.
Demographic changes and improvements in health care are projected to result in dramatic increases in the prevalence of dementia. Alzheimer's disease is widely considered to be the primary cause of dementia - a disease for which there is currently no cure nor effective treatment, and for which it is thought that little can be done to mitigate risk. ⋯ We also describe how active stimulation of the brain throughout the life course builds cognitive reserve that can offset or compensate for cognitive decline in later life. Finally, we discuss the implications of these emerging approaches for dementia prevention and advocate for the urgent implementation of more extensive public health strategies to improve vascular health.
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Frontiers in neurology · Jan 2013
Evidence That the Blood Biomarker SNTF Predicts Brain Imaging Changes and Persistent Cognitive Dysfunction in Mild TBI Patients.
Although mild traumatic brain injury (mTBI), or concussion, is not typically associated with abnormalities on computed tomography (CT), it nevertheless causes persistent cognitive dysfunction for many patients. Consequently, new prognostic methods for mTBI are needed to identify at risk cases, especially at an early and potentially treatable stage. Here, we quantified plasma levels of the neurodegeneration biomarker calpain-cleaved αII-spectrin N-terminal fragment (SNTF) from 38 participants with CT-negative mTBI, orthopedic injury (OI), and normal uninjured controls (UCs) (age range 12-30 years), and compared them with findings from diffusion tensor imaging (DTI) and long-term cognitive assessment. ⋯ The elevation in plasma SNTF in the subset of OI cases, accompanied by corresponding white matter and cognitive abnormalities, raises the possibility of identifying undiagnosed cases of mTBI. These data suggest that the blood level of SNTF on the day of a CT-negative mTBI may identify a subset of patients at risk of white matter damage and persistent disability. SNTF could have prognostic and diagnostic utilities in the assessment and treatment of mTBI.
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Frontiers in neurology · Jan 2013
Clostridium difficile Associated Disease in a Neurointensive Care Unit.
Critically ill patients are at high risk for acquiring Clostridium difficile infection. The aim of this study was to investigate the prevalence, severity, and outcome of neurointensive care unit (NICU) acquired Clostridium difficile associated disease (CDAD). ⋯ The prevalence rate (0.4%) and morbidity of CDAD in the unit are low. A larger database is needed to better analyze the associated risk factors in this subgroup of patients. A possible increase in disease burden due to a delay in discharge from the ICU merits further evaluation.