Fluid Biomarkers for Synaptic Dysfunction and Loss

Elena Camporesi; Johanna Nilsson; Ann Brinkmalm; Bruno Becker; Nicholas J Ashton; Kaj Blennow; Henrik Zetterberg

doi:10.1177/1177271920950319

Fluid Biomarkers for Synaptic Dysfunction and Loss

Biomark Insights. 2020 Aug 21:15:1177271920950319. doi: 10.1177/1177271920950319. eCollection 2020.

Authors

Elena Camporesi¹, Johanna Nilsson¹, Ann Brinkmalm¹, Bruno Becker^{1

2}, Nicholas J Ashton^{1

3

4

5}, Kaj Blennow^{1

2}, Henrik Zetterberg^{1

2

6

7}

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
³ King's College London, Institute of Psychiatry, Psychology & Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁴ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁵ Wallenberg Centre for Molecular and Translational Medicine, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
⁷ UK Dementia Research Institute at UCL, London, UK.

Abstract

Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders with reduced levels of pre- and postsynaptic proteins being recognized as a core feature of Alzheimer's disease (AD) pathophysiology. Together with AD, other neurodegenerative and neurodevelopmental disorders show altered synaptic homeostasis as an important pathogenic event, and due to that, they are commonly referred to as synaptopathies. The exact mechanisms of synapse dysfunction in the different diseases are not well understood and their study would help understanding the pathogenic role of synaptic degeneration, as well as differences and commonalities among them and highlight candidate synaptic biomarkers for specific disorders. The assessment of synaptic proteins in cerebrospinal fluid (CSF), which can reflect synaptic dysfunction in patients with cognitive disorders, is a keen area of interest. Substantial research efforts are now directed toward the investigation of CSF synaptic pathology to improve the diagnosis of neurodegenerative disorders at an early stage as well as to monitor clinical progression. In this review, we will first summarize the pathological events that lead to synapse loss and then discuss the available data on established (eg, neurogranin, SNAP-25, synaptotagmin-1, GAP-43, and α-syn) and emerging (eg, synaptic vesicle glycoprotein 2A and neuronal pentraxins) CSF biomarkers for synapse dysfunction, while highlighting possible utilities, disease specificity, and technical challenges for their detection.

Keywords: Alzheimer’s disease; Synaptic biomarkers; cerebrospinal fluid; proteomics; synaptopathies.

Publication types

Review