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Cell Mol Life Sci. 2019 May;76(10):1833-1863. doi: 10.1007/s00018-019-03040-5. Epub 2019 Feb 15.

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

Dhiman K1, Blennow K2,3, Zetterberg H2,3,4,5, Martins RN1,6,7,8,9, Gupta VB10,11.

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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.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
UK Dementia Research Institute, London, UK.
Australian Alzheimer's Research Foundation, Ralph and Patricia Sarich Neuroscience Research Institute, 8 Verdun Street, Nedlands, WA, Australia.
Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.
KaRa Institute of Neurological Diseases, Sydney, NSW, Australia.
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.
School of Medicine, Deakin University, Geelong, 3220, VIC, Australia.


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.


Diagnosis; Fatty acid-binding proteins; Neurodegeneration; Neurofilament light; Neurogranin; Neuroinflammation; Synaptic dysfunction

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