Transitioning from cerebrospinal fluid to blood tests to facilitate diagnosis and disease monitoring in Alzheimer's disease |
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Authors: | D. O. T. Alawode A. J. Heslegrave N. J. Ashton T. K. Karikari J. Simrén L. Montoliu-Gaya J. Pannee A. O´Connor P. S. J. Weston J. Lantero-Rodriguez A. Keshavan A. Snellman J. Gobom R. W. Paterson J. M. Schott K. Blennow N. C. Fox H. Zetterberg |
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Affiliation: | 1. From the, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK;2. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;3. UK Dementia Research Institute at UCL, London, UK;4. Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK |
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Abstract: | Alzheimer’s disease (AD) is increasingly prevalent worldwide, and disease-modifying treatments may soon be at hand; hence, now, more than ever, there is a need to develop techniques that allow earlier and more secure diagnosis. Current biomarker-based guidelines for AD diagnosis, which have replaced the historical symptom-based guidelines, rely heavily on neuroimaging and cerebrospinal fluid (CSF) sampling. While these have greatly improved the diagnostic accuracy of AD pathophysiology, they are less practical for application in primary care, population-based and epidemiological settings, or where resources are limited. In contrast, blood is a more accessible and cost-effective source of biomarkers in AD. In this review paper, using the recently proposed amyloid, tau and neurodegeneration [AT(N)] criteria as a framework towards a biological definition of AD, we discuss recent advances in biofluid-based biomarkers, with a particular emphasis on those with potential to be translated into blood-based biomarkers. We provide an overview of the research conducted both in CSF and in blood to draw conclusions on biomarkers that show promise. Given the evidence collated in this review, plasma neurofilament light chain (N) and phosphorylated tau (p-tau; T) show particular potential for translation into clinical practice. However, p-tau requires more comparisons to be conducted between its various epitopes before conclusions can be made as to which one most robustly differentiates AD from non-AD dementias. Plasma amyloid beta (A) would prove invaluable as an early screening modality, but it requires very precise tests and robust pre-analytical protocols. |
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Keywords: | Alzheimer's disease Blood Cerebrospinal fluid Diagnosis Disease monitoring Fluid biomarkers |
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