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Fluid-based proteomics targeted on pathophysiological processes and pathologies in neurodegenerative diseases

Brinkmalm, A; Portelius, E; Brinkmalm, G; Pannee, J; Dahlén, R; Gobom, J; Blennow, K; (2019) Fluid-based proteomics targeted on pathophysiological processes and pathologies in neurodegenerative diseases. Journal of Neurochemistry , 151 (4) pp. 417-434. 10.1111/jnc.14594. Green open access

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Abstract

Neurodegenerative dementias constitute a broad group of diseases in which abnormally folded proteins accumulate in specific brain regions and result in tissue reactions that eventually cause neuronal dysfunction and degeneration. Depending on where in the brain this happens, symptoms appear which may be used to classify the disorders on clinical grounds. However, brain changes in neurodegenerative dementias start to accumulate many years prior to symptom onset and there is a poor correlation between the clinical picture and what pathology that is the most likely to cause it. Thus novel drug candidates having disease-modifying effects, i.e., targeting the underlying pathology and changes the course of the disease needs to be defined using objective biomarker-based measures since the clinical symptoms are often non-specific and overlap between different disorders. Further, the treatment should ideally be initiated as soon as symptoms are evident or when biomarkers confirm an underlying pathology (pre-clinical phase of the disease) to reduce irreversible damage to, e.g., neurons, synapses and axons. Clinical trials in the pre-clinical phase bring a greater importance to biomarkers since by definition the clinical effects are difficult or slow to discern in a population that is not yet clinically affected. Here, we discuss neuropathological changes that may underlie neurodegenerative dementias, including how they can be detected and quantified using currently available bio fluid-based biomarkers and how more of them could be identified using targeted proteomics approaches. This article is protected by copyright. All rights reserved.

Type: Article
Title: Fluid-based proteomics targeted on pathophysiological processes and pathologies in neurodegenerative diseases
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/jnc.14594
Publisher version: http://doi.org/10.1111/jnc.14594
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: CSF, Alzheimer's disease, Neurodegeneration, TDP-43, amyloid, biomarkers, mass spectrometry, neurofilament, neurogranin, plasma, proteomics, serum, tau
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10061203
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