OBJECTIVE: The Lrrk2 kinase domain G2019S substitution is the most common genetic basis of familial and sporadic parkinsonism. Patients harboring the G2019S substitution usually present with clinical Parkinson's disease. METHODS: Herein, we report that the most common neuropathology of G2019S-associated Parkinson's disease is Lewy body disease. RESULTS: Lrrk2 G2019S was observed in approximately 2% (n = 8) of our Parkinson's disease/Lewy body disease cases (n = 405). The mutation was also found in one control subject and one Alzheimer's disease patient, reflecting reduced penetrance. INTERPRETATION: Therapeutic strategies targeted at modulating Lrrk2 kinase activity may be important to treat patients with genetically defined familial or typical sporadic Parkinson's disease.
OBJECTIVE: The Lrrk2 kinase domain G2019S substitution is the most common genetic basis of familial and sporadic parkinsonism. Patients harboring the G2019S substitution usually present with clinical Parkinson's disease. METHODS: Herein, we report that the most common neuropathology of G2019S-associated Parkinson's disease is Lewy body disease. RESULTS:Lrrk2G2019S was observed in approximately 2% (n = 8) of our Parkinson's disease/Lewy body disease cases (n = 405). The mutation was also found in one control subject and one Alzheimer's diseasepatient, reflecting reduced penetrance. INTERPRETATION: Therapeutic strategies targeted at modulating Lrrk2 kinase activity may be important to treat patients with genetically defined familial or typical sporadic Parkinson's disease.
Authors: Kenya Nishioka; Owen A Ross; Carles Vilariño-Güell; Stephanie A Cobb; Jennifer M Kachergus; David M A Mann; Julie Snowden; Anna M T Richardson; David Neary; Christopher A Robinson; Alex Rajput; Spiridon Papapetropoulos; Deborah C Mash; Rajesh Pahwa; Kelly E Lyons; Zbigniew K Wszolek; Dennis W Dickson; Matthew J Farrer Journal: Parkinsonism Relat Disord Date: 2011-01 Impact factor: 4.891
Authors: Christian Wider; Owen A Ross; Kenya Nishioka; Michael G Heckman; Carles Vilariño-Güell; Barbara Jasinska-Myga; Nilufer Erketin-Taner; Rosa Rademakers; Neill R Graff-Radford; Deborah C Mash; Spiridon Papapetropoulos; Ranjan Duara; Hirotake Uchikado; Zbigniew K Wszolek; Matthew J Farrer; Dennis W Dickson Journal: J Neurol Neurosurg Psychiatry Date: 2012-01-30 Impact factor: 10.154
Authors: Marta San Luciano; Richard B Lipton; Cuiling Wang; Mindy Katz; Molly E Zimmerman; Amy E Sanders; Laurie J Ozelius; Susan B Bressman; Rachel Saunders-Pullman Journal: Mov Disord Date: 2010-11-15 Impact factor: 10.338
Authors: R Saunders-Pullman; K Stanley; C Wang; M San Luciano; V Shanker; A Hunt; L Severt; D Raymond; L J Ozelius; R B Lipton; S B Bressman Journal: Neurology Date: 2011-07-13 Impact factor: 9.910
Authors: Michael G Heckman; Alexandra I Soto-Ortolaza; Monica Y Sanchez Contreras; Melissa E Murray; Otto Pedraza; Nancy N Diehl; Ronald Walton; Catherine Labbé; Oswaldo Lorenzo-Betancor; Ryan J Uitti; Jay van Gerpen; Nilüfer Ertekin-Taner; Glenn E Smith; Kejal Kantarci; Rodolfo Savica; David T Jones; Jonathan Graff-Radford; David S Knopman; Val J Lowe; Clifford R Jack; Ronald C Petersen; Joseph E Parisi; Rosa Rademakers; Zbigniew K Wszolek; Neill R Graff-Radford; Tanis J Ferman; Dennis W Dickson; Bradley F Boeve; Owen A Ross Journal: Parkinsonism Relat Disord Date: 2016-07-29 Impact factor: 4.891