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. 2025 Sep 24;272(10):651.
doi: 10.1007/s00415-025-13384-7.

Effect of aging on biomarkers and clinical profile in Parkinson's disease

Giulia Di Lazzaro  1   2 , Federico Paolini Paoletti  3 , Giovanni Bellomo  3 , Tommaso Schirinzi  4 , Piergiorgio Grillo  5   6 , Guido Maria Giuffrè  7   8 , Martina Petracca  7   8 , Anna Picca  7   9 , Nicola Biagio Mercuri  4 , Lucilla Parnetti  3 , Paolo Calabresi  7   8 , Anna Rita Bentivoglio  7   8
Affiliations

Effect of aging on biomarkers and clinical profile in Parkinson's disease

Giulia Di Lazzaro et al. J Neurol. .

Abstract

Background: Parkinson's disease (PD) has different progression rates and disease characteristics according to age of onset, the younger being less cognitively affected and experiencing more motor fluctuations. We explored different pathophysiologic mechanisms underlying PD in patients of different ages independently from disease duration, through CSF biomarkers.

Methods: Patients with clinically established diagnosis of PD underwent clinical evaluation through validated clinical scales (MDS-UPDRS, NMSS, MoCA, WOQ, QUIP, UDysRS). CSF inflammatory (YKL-40, TREM-2) and neurodegeneration (A-Beta42 and 40, t-Tau, p-Tau, NfL, Neurogranin, alpha-synuclein) biomarkers were analyzed.

Results: 95 PD patients were recruited, among whom 43 were younger than 66 years old, and 52 older. Age strongly correlated with neurofilament CSF levels, both light and heavy chain, with YKL-40 and with tau species. Younger and older patients showed different biomarker profiles. Younger patients showed significantly lower levels of inflammatory molecules (YKL-40), of degeneration biomarkers (tau species, neurofilament light and heavy chains), independently from disease duration. Clinically, younger patients had better scores at MDS-UPDRS parts I and III and were more prone to develop motor fluctuations and impulse control disorders.

Conclusions: Our data support the hypothesis that PD has different underlying biological features in younger and older subjects. Older subjects may have a broader spectrum of disease mechanisms, reflected in the higher prevalence of amyloid pathology and neurodegeneration, which could underlie the worse cognitive performances and lower dyskinesia burden. They could therefore necessitate a wider array of treatment strategies along with dopaminergic supplementation. Consequently, some of these biomarkers hold promise in refining treatment approaches in PD.

Keywords: Ageing; Fluid biomarkers; Parkinson’s disease.

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Conflict of interest statement

Declarations. Conflicts of interest: All authors declare no financial or non-financial competing interests. Ethical standard statement: This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and its subsequent amendments. The study protocol was reviewed and approved by the local Ethical Commitee of each center. All participants provided written informed consent prior to enrollment. Patient confidentiality was strictly maintained throughout the study in compliance with applicable data protection regulations. No identifying information is included in this publication.

Figures

Fig. 1
Fig. 1
Heath map showing correlations among CSF biomarkers
Fig. 2
Fig. 2
Correlations between age and CSF biomarkers and MDS-UPDRS III
Fig. 3
Fig. 3
CSF biomarkers differences in younger and older PD patients
See this image and copyright information in PMC

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