Fluid markers of synapse degeneration in synucleinopathies
Por:
Gonzalez, AC, Belbin, O
Publicada:
1 feb 2022
Ahead of Print:
1 feb 2022
Resumen:
The abnormal accumulation of alpha-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 alpha-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.
Filiaciones:
Gonzalez, AC:
Biomed Res Inst St Pau IIB St Pau, Neurol Dept, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, St Pau Memory Unit, Barcelona 08025, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
Belbin, O:
Biomed Res Inst St Pau IIB St Pau, Neurol Dept, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, St Pau Memory Unit, Barcelona 08025, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
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