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Biofluid Markers for Prodromal Parkinson's Disease: Evidence From a Catecholaminergic Perspective.

ABSTRACT: Parkinson's disease (PD) is the most frequent of all Lewy body diseases, a family of progressive neurodegenerative disorders characterized by intra-neuronal cytoplasmic inclusions of ?-synuclein. Its most defining features are bradykinesia, tremor, rigidity and postural instability. By the time PD manifests with motor signs, 70% of dopaminergic midbrain neurons are lost, and the disease is already in the middle or late stage. However, there are various non-motor symptoms occurring up to 20 years before the actual parkinsonism that are closely associated with profound deficiency of myocardial noradrenaline content and peripheral sympathetic denervation, as evidenced by neuroimaging experiments in recent years. Additionally, there is an inherent autotoxicity of catecholamines in the neuronal cells in which they are produced, forming toxic catecholaldehyde intermediates that make ?-synuclein prone to aggregation, initiating a cascade of events that ultimately leads to neuronal death. The etiopathogenesis of PD and related synucleinopathies thus may well be a prototypical example of a catecholamine-regulated neurodegeneration, given that the synucleinopathy in PD spreads in synergy with central and peripheral catecholaminergic dysfunction from the earliest phases onward. That is why catecholamines and their metabolites, precursors, or derivatives in cerebrospinal fluid or plasma could be of particular interest as biomarkers for prodromal and de novo PD. Because there is great demand for such markers, this mini-review summarizes all catecholamine-related studies to date, in addition to providing profound neurochemical evidence on a systemic and cellular level to further emphasize this hypothesis and with emphasis on extracellular vesicles as a novel diagnostic and therapeutic incentive.

SUBMITTER: Vermeiren Y

PROVIDER: S-EPMC7373724 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Biofluid Markers for Prodromal Parkinson's Disease: Evidence From a Catecholaminergic Perspective.

Vermeiren Yannick Y Hirschberg Yael Y Mertens Inge I De Deyn Peter P PP

Frontiers in neurology 20200715

Parkinson's disease (PD) is the most frequent of all Lewy body diseases, a family of progressive neurodegenerative disorders characterized by intra-neuronal cytoplasmic inclusions of α-synuclein. Its most defining features are bradykinesia, tremor, rigidity and postural instability. By the time PD manifests with motor signs, 70% of dopaminergic midbrain neurons are lost, and the disease is already in the middle or late stage. However, there are various non-motor symptoms occurring up to 20 years ...[more]

PMID: 32760338

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Project description:In Parkinson's disease, electroencephalographic abnormalities during wakefulness and non-rapid eye movement sleep (spindles) were found to be predictive biomarkers of dementia. Because rapid eye movement sleep is regulated by the cholinergic system, which shows early degeneration in Parkinson's disease with cognitive impairment, anomalies during this sleep stage might mirror dementia development. In this prospective study, we examined baseline electroencephalographic absolute spectral power across three states of consciousness (non-rapid eye movement sleep, rapid eye movement sleep, and wakefulness) in 68 non-demented patients with Parkinson's disease and 44 healthy controls. All participants underwent baseline polysomnographic recordings and a comprehensive neuropsychological assessment. Power spectral analyses were performed on standard frequency bands. Dominant occipital frequency during wakefulness and ratios of slow-to-fast frequencies during rapid eye movement sleep and wakefulness were also computed. At follow-up (an average 4.5 years after baseline), 18 patients with Parkinson's disease had developed dementia and 50 patients remained dementia-free. In rapid eye movement sleep, patients with Parkinson's disease who later developed dementia showed, at baseline, higher absolute power in delta and theta bands and a higher slowing ratio, especially in temporal, parietal, and occipital regions, compared to patients who remained dementia-free and controls. In non-rapid eye movement sleep, lower baseline sigma power in parietal cortical regions also predicted development of dementia. During wakefulness, patients with Parkinson's disease who later developed dementia showed lower dominant occipital frequency as well as higher delta and slowing ratio compared to patients who remained dementia-free and controls. At baseline, higher slowing ratios in temporo-occipital regions during rapid eye movement sleep were associated with poor performance on visuospatial tests in patients with Parkinson's disease. Using receiver operating characteristic curves, we found that best predictors of dementia in Parkinson's disease were rapid eye movement sleep slowing ratios in posterior regions, wakefulness slowing ratios in temporal areas, and lower dominant occipital frequency. These results suggest that electroencephalographic slowing during sleep is a new promising predictive biomarker for Parkinson's disease dementia, perhaps as a marker of cholinergic denervation.

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Biofluid Markers for Prodromal Parkinson's Disease: Evidence From a Catecholaminergic Perspective.

Publications

Biofluid Markers for Prodromal Parkinson's Disease: Evidence From a Catecholaminergic Perspective.

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