An international research team led by Prof Vincenzo Bonifati (Department of Clinical Genetics, Erasmus MC Rotterdam) has discovered for the first time variants in a gene linked to familial forms of Parkinson’s disease (PD), Parkinson’s disease Dementia (PDD), and Dementia with Lewy bodies (LBD). The discovery has been published the 7th of June on Lancet Neurology. The gene is named LRP10 (LDL Receptor Related Protein 10) and has been first identified in a large Italian family with 13 members affected by PD and 1 member affected by LBD. The researchers have subsequently demonstrated additional disease-associated LRP10 variants in patients from a large international multicentre series diagnosed with PD, PDD, LBD. Neuropathological studies, performed in 3 patients carrying different LRP10 variant, show severe accumulation of the alpha-synuclein protein. Loss of function of LRP10 has been proposed as a common pathogenic mechanism. The discovery of LRP10 variants links PD, PDD and LBD and opens novel window on mechanisms and might pave way to novel biomarkers.
This study is the result of an international collaboration, led by the Erasmus MC, Department of Clinical Genetics (team leader: Prof. Vincenzo Bonifati; senior scientists: Dr. Marialuisa Quadri and Dr. Wim Mandemakers), and involving among others, the Dept. of Neurology, Erasmus MC (Dr. Agnita Boon, Dr. Frank Jan de Jong, Prof. John van Swieten); the Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam (Dr. Wilma van de Berg); the Dipartimento di Scienze Biomediche e NeuroMotorie, University of Bologna, Italy (Prof Pietro Cortelli); the Department of Neurology and Psychiatry, University of Roma (Prof. Giuseppe Meco); the Neurology Service and Stroke Unit, Brotzu General Hospital, Cagliari, Italy (Dr. Giovanni Cossu); the Instituto de Medicina Molecular, University of Lisbon, Portugal (Dr. Joaquim Ferreira); and the Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (Prof. Chin-Song Lu).
Reference: Quadri et al, LRP10 genetic variants in familial Parkinson’s disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study. Lancet Neurology, 2018. Online 07 June 2018. DOI: https://doi.org/10.1016/S1474-4422(18)30179-0
by Dr Francesca Morgante (on behalf of the Scientific Panel Movement Disorders)
St. George’s University of London, UK
