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

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.