Dr. Jan O. Aasly studied medicine in Oslo, Norway, and earned his PhD at the University of Northern Sweden, Umeå, Sweden. He did his clinical training in neurology and clinical neurophysiology in Trondheim, Norway and Umeå, Sweden. He served as consultant neurologist at the University hospital in Tromsø, Norway and since 1989 in Trondheim; served as head of the Department of Neurology in Trondheim between 1992 and 1999. Since 1995 he has been a consultant neurologist and Professor of Neurology at the Department of Neurology at St. Olav’s Hospital, and the Norwegian University of Science and Technology, Trondheim, Norway. His main research topics have been speech, memory and hemispheric dominance in complex partial epilepsy; mitochondrial disorders and metabolic myopathies. During the last 25 years, Dr. Aasly´s main work has been longitudinal studies in Parkinson’s disease including genetics, biomarkers in PD, imaging and clinical studies. This has been possible through close collaboration within leading PD research centers world-wide, and though GEoPD. Furthermore, Trondheim is part of the MJ Fox supported PPMI project.
Reduced penetrance in Norwegian LRRK2 mutation carriers
LRRK2 mutations account for up to 20-30 % of Parkinson’s disease (PD) in the Middle East, and roughly 1% in Caucasian populations in the Western world. The prevalence of LRRK2 PD varies due to founder effects. The LRRK2 PD phenotype is similar to that of sporadic PD and most cases have a late disease onset. The histopathological findings are Lewy body pathology in only about half of the cases. Carriers of LRRK2 Gly2019Ser have incomplete penetrance. This may be explained by modifiers that modulate the phenoconversion of LRRK2 Gly2019Ser carriers, putatively by modulating the expression of other genes.
DNM3 appears to be a modifier of PD age of onset in LRRK2 Gly2019Ser carriers. DNM3 expression represents a target for neuroprotection in LRRK2 Gly2019Ser carriers and potentially for disease modification in affected individuals. There may also be other metabolic factors, which may be population specific and may explain the incomplete penetrance.
Imaging studies have demonstrated that healthy LRRK2 mutation carriers show metabolic changes in the basal ganglia 10-15 years prior to phenoconversion. Subtle clinical findings are relatively easy to demonstrate in parallel to imaging pathology. There are no other biomarkers available. Aspects of basic mechanisms in LRRK2 and other monogenic PDs will be discussed.