Espay AJ, Lafontant DE, Poston KL, et al. - In Parkinson disease, lower total brain volume in relation to reduction in soluble amyloid-beta (Aβ42) was found.

• Parkinson Progression Markers Initiative participants were examined for 4-year change in total brain volume (n = 99) and baseline cerebrospinal fluid (CSF) alpha-synuclein (α‐syn), Aβ42, phosphorylated tau, and total tau.

• The 4-year change in total brain volume was not significantly associated with baseline levels of any CSF biomarker.

• A linear association of CSF Aβ42 with total brain volume at baseline (R ² = 0.60) and at year 2 (R ² = 0.66) was evident in cross-sectional analyses.

• In addition, smaller total brain volume at baseline and at year 2 was observed in relation to CSF Aβ42 < 1100 pg/ml (the threshold for brain amyloid pathology).

• There was a linear relationship of CSF α‐syn with total brain volume at baseline (R ² = 0.58) but not at year 2 (R ² = 0.58).