Jan Aaseth (Norway)
Innlandet Hospital Trust Research DepartmentAuthor Of 1 Presentation
CSF, BLOOD AND MRI BIOMARKERS IN A RARE NEURODEGENERATIVE DISEASE IN A NORWEGIAN KINDRED
Abstract
Aims
Skogholt disease is a rare central and peripheral neurodegenerative disorder only observed with maternal inheritance in a small Norwegian family line. The clinical symptoms develop between ages 30 and 70 in affected family members and include cognitive decline, progressive muscle weakness, unsteady gait, and dysarthria. Brain imaging reveals extensive white matter hyperintensities (WMHs), and CSF protein and several other CSF biomarkers are greatly elevated. Herein, our objective was to further study Skogholt disease pathology.
Methods
We analyzed blood and CSF biomarkers in eleven Skogholt cases and fourteen lab-controls. T1-weighted and FLAIR MRI were performed on cases and sixty controls. Cortical reconstruction and volumetric segmentation were performed with the FreeSurfer image analysis suite version 6. (http://surfer.nmr.mgh.harvard.edu/). WMH volume was assessed with an in-house deep-learning-based algorithm.
Results
Compared to controls, we found increased CSF levels of all examined Aβ species, T-tau, P-tau, GFAP, β-trace protein, PDGFRb and total protein, but not NFL. There were no differences in blood biomarkers. The CSF Aβ42/40 ratio was pathological, and after adjusting for CSF total protein, CSF Aβ42 was decreased. Compared to controls, Skogholt cases had thicker cerebral cortices, smaller ventricles and total white matter volume, and higher WMH volume. CSF opening pressure was normal in all cases. Figures 1-3 show biomarker differences between Skogholt cases and controls.
Conclusions
The cause for the strikingly unusual combination of clinical and paraclinical findings in Skogholt disease is unknown but likely genetic. Candidate mechanisms relate to dysmyelination and small vessel disease with blood-brain barrier disruption. Further investigations are warranted, and we are preparing a detailed longitudinal study.