Erasmus MC Press Release Rotterdam, 08 June 2018
New gene involved in the development of Parkinson’s disease and dementia with Lewy bodies
Discovery opens novel window on mechanisms and might pave way to novel biomarkers
An international team led by Prof. Vincenzo Bonifati from the Erasmus MC Rotterdam, Department of Clinical Genetics, has discovered for the first time variants in a gene (termed LRP10) in patients with familial forms of Parkinson’s disease, Parkinson’s disease and dementia, and Dementia with Lewy bodies. The paper reporting this discovery will be published in The Lancet Neurology this week. ‘This discovery opens a novel window on the molecular mechanisms of these common neurodegenerative diseases, and might pave the way to the identification of novel biomarkers and novel disease-modifying therapies’, says Prof. Bonifati.
Parkinson's disease and Dementia are common and devastating neurodegenerative diseases. Only symptomatic remedies are available, but not disease-modifying or curative therapies exist. Besides, the prevalence of these diseases is expected to increase in the future decades due to the aging of the populations of the world. These diseases pose therefore a huge medical and economic burden to the society.

The research team identified the first LRP10 gene variant by clinical and genetic studies in a large family with multiple people affected by Parkinson’s disease. They subsequently detected additional disease-associated LRP10 variants in patients from a large international multicentre series diagnosed either clinically or pathologically with Parkinson’s disease, Parkinson’s disease dementia, or dementia with Lewy bodies. They also carried out brain pathology studies in three patients, each of these carrying different disease-associated LRP10 variants, showing a severe accumulation of the alpha-synuclein protein, the pathologic hallmark of these diseases. Last, they did in-vitro studies using neuronal cellular models obtained by human pluripotent stem-like cells, to analyse the protein encoded by the LRP10 gene, its cellular localization, and the effect of the variants found in the patients.

Very little is known about the normal function of LRP10, and a role for this gene in the development of Parkinson’s disease and dementia with Lewy bodies was unknown so far. Elucidating the cellular function of the LRP10 protein and its signalling pathways could offer novel and crucial insights into the molecular mechanisms of these common neurodegenerative diseases, and hopefully pave the way to the identification of novel biomarkers and novel targets for disease-modifying therapies.

This discovery 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).

This research was supported by the Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw—Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson’s UK, Avtal om Läkarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands–Ligue Européene Contre la Maladie d’Alzheimer (LECMA).

Prof. Vincenzo Bonifati, a neurologist and geneticist, has a long-term research interest in elucidating the genetic bases of Parkinson’s disease and other neurodegenerative disorders. He has authored more than 180 research papers, which have been cited so far more than 13,000 times in the scientific literature, and he has an H-index of 58 (source: Scopus)
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