Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807
ABSTRACT Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimer's disease. We have developed a novel PHF-tau targeting positron emission tomography imaging agent, [F-18]-T807, which may be useful for imaging Alzheimer's disease and other tauopathies. Here, we describe the first human brain images with [F-18]-T807.
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ABSTRACT: The military conflicts of the last decade have highlighted the growing problem of traumatic brain injury in combatants returning from the battlefield. The considerable evidence pointing at the accumulation of tau aggregates and its recognition as a risk factor in neurodegenerative conditions such as Alzheimer's disease have led to a major effort to develop selective tau ligands that would allow research into the physiopathologic underpinnings of traumatic brain injury and chronic traumatic encephalopathy in military personnel and the civilian population. These tracers will allow new insights into tau pathology in the human brain, facilitating research into causes, diagnosis, and treatment of traumatic encephalopathy and major neurodegenerative dementias, such as Alzheimer's disease and some variants of frontotemporal lobar degeneration, in which tau plays a role. The field of selective tau imaging has to overcome several obstacles, some of them associated with the idiosyncrasies of tau aggregation and others related to radiotracer design. A worldwide effort has focused on the development of imaging agents that will allow selective tau imaging in vivo. Recent progress in the development of these tracers is enabling the noninvasive assessment of the extent of tau pathology in the brain, eventually allowing the quantification of changes in tau pathology over time and its relation to cognitive performance, brain volumetrics, and other biomarkers, as well as assessment of efficacy and patient recruitment for antitau therapeutic trials.Alzheimer's and Dementia 06/2014; 10(3):S254–S264. DOI:10.1016/j.jalz.2014.04.013 · 17.47 Impact Factor
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ABSTRACT: Over the past decade, public awareness of the long-term pathological consequences of traumatic brain injury (TBI) has increased. Such awareness has been stimulated mainly by reports of progressive neurological dysfunction in athletes exposed to repetitive concussions in high-impact sports such as boxing and American football, and by the rising number of TBIs in war veterans who are now more likely to survive explosive blasts owing to improved treatment. Moreover, the entity of chronic traumatic encephalopathy (CTE)-which is marked by prominent neuropsychiatric features including dementia, parkinsonism, depression, agitation, psychosis, and aggression-has become increasingly recognized as a potential late outcome of repetitive TBI. Annually, about 1% of the population in developed countries experiences a clinically relevant TBI. The goal of this Review is to provide an overview of the latest understanding of CTE pathophysiology, and to delineate the key issues that are challenging clinical and research communities, such as accurate quantification of the risk of CTE, and development of reliable biomarkers for single-incident TBI and CTE.Nature Reviews Neurology 04/2013; 9(4):192-200. DOI:10.1038/nrneurol.2013.36 · 14.10 Impact Factor
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ABSTRACT: Abstract The term frontotemporal dementia (FTD) refers to a group of neurodegenerative disorders that are associated with atrophy of the frontal and temporal lobes, and present clinically with impairments of behaviour or language. Three main subtypes are described, behavioural variant FTD (bvFTD) and two subtypes of the language presentation (known as primary progressive aphasia or PPA) called semantic variant of PPA and non-fluent variant of PPA. Most imaging studies of FTD have used volumetric T1 magnetic resonance imaging (MRI) or positron emissions tomography imaging to identify patterns of grey matter atrophy or hypometabolism in these different subtypes, but more recently newer imaging techniques have been used to help define abnormalities in structural connectivity (white matter tract integrity using diffusion tensor imaging), functional connectivity (resting state networks using resting state functional MRI) and perfusion (using arterial spin labelling perfusion MRI) in FTD. These techniques have the potential to improve the differential diagnosis of FTD from other disorders and to provide more informative imaging signatures of FTD syndromes.International Review of Psychiatry 04/2013; 25(2):221-9. DOI:10.3109/09540261.2013.778822 · 1.80 Impact Factor