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Cerebrospinal fluid biomarkers for understanding multiple aspects of Alzheimer's disease pathogenesis

Dhiman, K; Blennow, K; Zetterberg, H; Martins, RN; Gupta, VB; (2019) Cerebrospinal fluid biomarkers for understanding multiple aspects of Alzheimer's disease pathogenesis. Cellular and Molecular Life Sciences , 76 pp. 1833-1863. 10.1007/s00018-019-03040-5. Green open access

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Abstract

Alzheimer's disease (AD) is a multifactorial age-related brain disease. Numerous pathological events run forth in the brain leading to AD. There is an initial long, dormant phase before the clinical symptoms become evident. There is a need to diagnose the disease at the preclinical stage since therapeutic interventions are most likely to be effective if initiated early. Undoubtedly, the core cerebrospinal fluid (CSF) biomarkers have a good diagnostic accuracy and have been used in clinical trials as end point measures. However, looking into the multifactorial nature of AD and the overlapping pathology with other forms of dementia, it is important to integrate the core CSF biomarkers with a broader panel of other biomarkers reflecting different aspects of pathology. The review is focused upon a panel of biomarkers that relate to different aspects of AD pathology, as well as various studies that have evaluated their diagnostic potential. The panel includes markers of neurodegeneration: neurofilament light chain and visinin-like protein (VILIP-1); markers of amyloidogenesis and brain amyloidosis: apolipoproteins; markers of inflammation: YKL-40 and monocyte chemoattractant protein 1; marker of synaptic dysfunction: neurogranin. These markers can highlight on the state and stage-associated changes that occur in AD brain with disease progression. A combination of these biomarkers would not only aid in preclinical diagnosis, but would also help in identifying early brain changes during the onset of disease. Successful treatment strategies can be devised by understanding the contribution of these markers in different aspects of disease pathogenesis.

Type: Article
Title: Cerebrospinal fluid biomarkers for understanding multiple aspects of Alzheimer's disease pathogenesis
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00018-019-03040-5
Publisher version: https://doi.org/10.1007/s00018-019-03040-5
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: Diagnosis, Fatty acid-binding proteins, Neurodegeneration, Neurofilament light, Neurogranin, Neuroinflammation, Synaptic dysfunction
UCL classification: UCL
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/10069673
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