Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Mar 17;15(3):65.
doi: 10.3390/clinpract15030065.

A Narrative Review on Biochemical Markers and Emerging Treatments in Prodromal Synucleinopathies

Jamir Pitton Rissardo  1 , Ana Leticia Fornari Caprara  1
Affiliations
Review

A Narrative Review on Biochemical Markers and Emerging Treatments in Prodromal Synucleinopathies

Jamir Pitton Rissardo et al. Clin Pract. .

Abstract

Alpha-synuclein has been associated with neurodegeneration, especially in Parkinson's disease (PD). This study aimed to review clinical, biochemical, and neuroimaging markers and management of prodromal synucleinopathies. The prodromal state of synucleinopathies can be better understood with PD pathophysiology, and it can be separated into premotor and pre-diagnostic phases. The incidence of PD in patients with prodromal phase symptoms ranges from 0.07 to 14.30, and the most frequently studied pathology is the REM behavioral disorder (RBD). Neuroimaging markers are related to dopamine denervation, brain perfusion changes, gross anatomy changes, and peripheral abnormalities. α-synuclein assays (SAA) in CSF revealed high sensitivity (up to 97%) and high specificity (up to 92%); in the last decade, there was the development of other matrices (blood, skin, and olfactory mucosa) for obtaining quantitative and qualitative α-synuclein. Other biomarkers are neurofilament light chain, DOPA decarboxylase, and multiplexed mass spectrometry assay. Regarding genetic counseling in α-synucleinopathies, it is an important topic in clinical practice to discuss with patients with high-risk individuals and should involve basic principles of autonomy, beneficence, and non-maleficence. Some of the themes that should be reviewed are the involvement of physical activity, diet (including alcohol, coffee, and vitamin supplementation), smoking, sleep, and stress in the pathophysiology of synucleinopathies. The number of trials related to prodromal symptoms is still scarce, and the number of studies evaluating intervention is even lower.

Keywords: Parkinson’s disease; RBD; alpha-synuclein; biofluid; prevention; prodromal; synucleinopathies.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Stages of Parkinson’s disease with biomarkers. Dopaminergic loss and noradrenergic denervation can be observed. Also, the Braak staging and Lewy body pathology can be linked to the stages.
Figure 2
Figure 2
Movement Disorder Society research criteria for prodromal multiple system atrophy (MSA) and Parkinson’s disease (PD). Abbreviations: DMS, Diagnostic and Statistical Manual of Mental; OH, orthostatic hypotension; PSP, Progressive Supranuclear Palsy; RBD, REM sleep behavior disorder.
Figure 3
Figure 3
Strategic questions of the Parkinson Progression Marker Initiative (PPMI) study.
Figure 4
Figure 4
WHO Exercise recommendation for adults with living disabilities (including PD).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Mavroeidi P., Xilouri M. Neurons and Glia Interplay in α-Synucleinopathies. Int. J. Mol. Sci. 2021;22:4994. doi: 10.3390/ijms22094994. - DOI - PMC - PubMed
    1. Postuma R.B., Berg D. Advances in Markers of Prodromal Parkinson Disease. Nat. Rev. Neurol. 2016;12:622–634. doi: 10.1038/nrneurol.2016.152. - DOI - PubMed
    1. Braak H., Del Tredici K., Rüb U., de Vos R.A.I., Jansen Steur E.N.H., Braak E. Staging of Brain Pathology Related to Sporadic Parkinson’s Disease. Neurobiol. Aging. 2003;24:197–211. doi: 10.1016/S0197-4580(02)00065-9. - DOI - PubMed
    1. Khalil I., Sayad R., Kedwany A.M., Sayed H.H., Caprara A.L.F., Rissardo J.P. Cardiovascular Dysautonomia and Cognitive Impairment in Parkinson’s Disease (Review) Med. Int. 2024;4:70. doi: 10.3892/mi.2024.194. - DOI - PMC - PubMed
    1. Isaias I.U., Marotta G., Pezzoli G., Sabri O., Schwarz J., Crenna P., Classen J., Cavallari P. Enhanced Catecholamine Transporter Binding in the Locus Coeruleus of Patients with Early Parkinson Disease. BMC Neurol. 2011;11:88. doi: 10.1186/1471-2377-11-88. - DOI - PMC - PubMed

LinkOut - more resources