Low soluble amyloid-β 42 is associated with smaller brain volume in Parkinson's disease

Abstract

Introduction: We sought to examine whether levels of soluble alpha-synuclein (α-syn), amyloid-beta (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau), as measured in cerebrospinal fluid (CSF), are associated with changes in brain volume in Parkinson's disease.

Methods: We assessed the 4-year change in total brain volume (n = 99) and baseline CSF α-syn, Aβ42, p-tau, and t-tau of Parkinson Progression Markers Initiative participants. We used linear mixed models to assess the longitudinal effect of baseline CSF biomarkers on total and regional brain volume and thickness as well as linear regression for cross-sectional analyses at baseline and year 2. All models were adjusted for age and gender; brain volume models also adjusted for baseline intracranial volume. Bonferroni correction was applied.

Results: The 4-year change in total brain volume was -21.2 mm³ (95% confidence interval, -26.1, -16.3). There were no significant associations between the 4-year change in total brain volume and baseline levels of any CSF biomarker (all p-values > 0.05). On cross-sectional analyses, CSF Aβ42 was linearly associated with total brain volume at baseline (R² = 0.60, p = 0.0004) and at year 2 (R² = 0.66, p < 0.0001), with CSF Aβ42 < 1100 pg/ml, the threshold for brain amyloid pathology, associated with smaller total brain volume at baseline (p = 0.0010) and at year 2 (p = 0.0002). CSF α-syn was linearly associated with total brain volume at baseline (R² = 0.58, p = 0.0044) but not at year 2 (R² = 0.58, p = 0.1342).

Conclusion: Reduction in soluble Aβ42 is associated with lower total brain volume in Parkinson's disease.

Keywords: Alpha-synuclein; Amyloid; Biomarkers; Clinico-pathologic; Parkinson's disease.