Fig. 6

Increased neurofilament immunoreactivity is associated with pathology load and MRI biomarkers of neurodegeneration in PD. Middle panel: neurofilament immunoreactivity is increased in both PD and PDD/DLB cortex. Specifically, increased NfM/H phosphorylation occurs across the cortex in both PD and PDD/DLB (blue square), possibly indicating axonal stress, and is associated with increased p-tau load (left panel, blue arrow). On the other hand, an increased NfL immunoreactivity, representing NfL accumulation in disease neurons and fragmented axons, is observed in the entorhinal cortex and parahippocampal gyrus of PDD/DLB donors (red square) and associated with LB count and p-tau load (left panel, red arrow), suggesting structural changes with increasing pathological burden, and confirming its important role in the context of cognitive decline. Right panel: both increased p-NfM/H (i.e. axonal stress) and NfL immunoreactivity (i.e. NfL accumulation and fragmentation) are reflected by cortical thinning in PD and increased cortical MD in PDD/DLB. Figure created with BioRender.com. DLB: Dementia with Lewy Bodies; LB: Lewy Body; NfL: neurofilament light chain; PD: Parkinson’s disease; PDD: Parkinson’s disease dementia; NfM/H: phosphorylated neurofilament medium and heavy chain; p-tau: phosphorylated tau