Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 76, Issue 10, Pages 1833-1863Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-019-03040-5
Keywords
Diagnosis; Neurofilament light; Neurodegeneration; Synaptic dysfunction; Neurogranin; Fatty acid-binding proteins; Neuroinflammation
Categories
Funding
- CogState Ltd.
- Sir Charles Gairdner Hospital
- National Health and Medical Research Council (NHMRC)
- Brightfocus Foundation USA
- Dementia Australia Dementia Research Foundation (AADRF)
- Dementia Collaborative Research Centres program (DCRC2)
- Cooperative Research Centre (CRC) for Mental Health
- McCusker Alzheimer's Research Foundation
- ECU HDR (Higher degree by research) Scholarship
- Torsten Soderberg foundation, Sweden
- Swedish Research Council
- European Research Council
- Olav Thon Foundation
- UK Dementia Research Institute at UCL
- Government of Victoria
- Hollywood Private Hospital
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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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