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

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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.

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Acknowledgements

The authors thank the Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL) Study Group (http://www.aibl.csiro.au) Edith Cowan University (ECU) and Deakin University. The AIBL study is a collaboration between Commonwealth Scientific and Industrial Research Organisation (CSIRO), ECU, The Florey Institute of Neuroscience and Mental Health (FINMH), National Ageing Research Institute (NARI), and Austin Health. It involves support from CogState Ltd., Hollywood Private Hospital, and Sir Charles Gairdner Hospital. The study receives funding from the National Health and Medical Research Council (NHMRC), Brightfocus Foundation USA, Dementia Australia Dementia Research Foundation (AADRF), the Dementia Collaborative Research Centres program (DCRC2), the Cooperative Research Centre (CRC) for Mental Health, the McCusker Alzheimer’s Research Foundation and Operational Infrastructure Support from the Government of Victoria. KD also thanks ECU HDR (Higher degree by research) Scholarship. KB is supported by the Torsten Söderberg foundation, Sweden. HZ is a Wallenberg Academy Fellow supported by grants from the Swedish Research Council, the European Research Council, the Olav Thon Foundation and the UK Dementia Research Institute at UCL.

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Authors and Affiliations

  1. Centre of Excellence in Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA, Australia

    Kunal Dhiman, Ralph N. Martins & Veer Bala Gupta

  2. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden

    Kaj Blennow & Henrik Zetterberg

  3. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

    Kaj Blennow & Henrik Zetterberg

  4. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK

    Henrik Zetterberg

  5. UK Dementia Research Institute, London, UK

    Henrik Zetterberg

  6. Australian Alzheimer’s Research Foundation, Ralph and Patricia Sarich Neuroscience Research Institute, 8 Verdun Street, Nedlands, WA, Australia

    Ralph N. Martins

  7. Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia

    Ralph N. Martins

  8. School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia

    Ralph N. Martins

  9. KaRa Institute of Neurological Diseases, Sydney, NSW, Australia

    Ralph N. Martins

  10. School of Medicine, Deakin University, Geelong, 3220, VIC, Australia

    Veer Bala Gupta

Authors
  1. Kunal Dhiman
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  2. Kaj Blennow
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  3. Henrik Zetterberg
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  4. Ralph N. Martins
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  5. Veer Bala Gupta
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Corresponding author

Correspondence to Veer Bala Gupta.

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Conflict of interest

KB has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Novartis, Pfizer, and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. HZ has served at scientific advisory boards of Eli Lilly, Roche Diagnostics, Samumed, CogRx and Wave, has received travel support from Teva and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg.

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Dhiman, K., Blennow, K., Zetterberg, H. et al. Cerebrospinal fluid biomarkers for understanding multiple aspects of Alzheimer’s disease pathogenesis. Cell. Mol. Life Sci. 76, 1833–1863 (2019). https://doi.org/10.1007/s00018-019-03040-5

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  • DOI: https://doi.org/10.1007/s00018-019-03040-5

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