Cited by 7Parkinson's Disease Mechanisms and TreatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Fluid markers of synapse degeneration in synucleinopathies

Cervantes González, Alba, Belbin, Olivia·2022·Journal of Neural Transmission

Abstract

The abnormal accumulation of α-synuclein in the brain is a common feature of Parkinson's disease (PD), PD dementia (PDD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), and synucleinopathies that present with overlapping but distinct clinical symptoms that include motor and cognitive deficits. Synapse degeneration is the crucial neuropathological event in these synucleinopathies and the neuropathological correlate of connectome dysfunction. The cognitive and motor deficits resulting from the connectome dysfunction are currently measured by scalar systems that are limited in their sensitivity and largely subjective. Ideally, a marker of synapse degeneration would correlate with measures of cognitive or motor impairment, and could therefore be used as a more objective, surrogate biomarker of the core clinical features of these diseases. Furthermore, an objective surrogate biomarker that can detect and monitor the progression of synapse degeneration would improve patient management and clinical trial design, and could provide a measure of therapeutic response. Here, we review the published findings relating to candidate biomarkers of synapse degeneration in PD, PDD, DLB, and MSA patient-derived biofluids and discuss the findings in the context of the mechanisms associated with α-synuclein-mediated synapse degeneration. Understanding these mechanisms is essential not only for discovery of biomarkers, but also to improve our understanding of the earliest changes in disease pathogenesis of synucleinopathies.

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Crossref · 10.1007/s00702-022-02467-8

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Authors
Cervantes González, A., & Belbin, O.
Affiliations
Hospital de Sant Pau (ES)
Corresponding author
Belbin, Olivia
Venue
Journal of Neural Transmission
Published
2022-02
Volume
129
Issue
2
Pages
187-206
ISSN
  • 0300-9564 (ISSN-L)
  • 1435-1463
OpenAlex
W4211017991
Cited by
7
References
149
Citations by year
2025: 2 · 2023: 4 · 2022: 1
FWCI
0.25
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neural Transmission (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Instituto de Salud Carlos III (PI18/00327)
  • Agència de Gestió d’Ajuts Universitaris i de Recerca (2019 PROD 000088)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
synaptic degeneration, synucleinopathies, alpha-synuclein, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, multiple system atrophy, biomarkers, biological fluids, disease progression, treatment response monitoring
MeSH terms
Synucleinopathies, Humans, Synapses, Biomarkers, Multiple System Atrophy, Lewy Body Disease, alpha-Synuclein

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