Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease
- Lorraine V Kalia 1, Anthony E Lang 1, Lili-Naz Hazrati 2, Shinsuke Fujioka 3, Zbigniew K Wszolek 3, Dennis W Dickson 3, Owen A Ross 3, Vivianna M Van Deerlin 4, John Q Trojanowski 4, Howard I Hurtig 4, Roy N Alcalay 5, Karen S Marder 5, Lorraine N Clark 5, Carles Gaig 6, Eduardo Tolosa 6, Javier Ruiz-Martínez 7, Jose F Marti-Masso 7, Isidre Ferrer 8, Adolfo López de Munain 7, Samuel M Goldman 9, Birgitt Schüle 10, J William Langston 10, Jan O Aasly 11, Maria T Giordana 12, Vincenzo Bonifati 13, Andreas Puschmann 14, Margherita Canesi 15, Gianni Pezzoli 15, Andre Maues De Paula 16, Kazuko Hasegawa 17, Charles Duyckaerts 18, Alexis Brice 18, A Jon Stoessl 19, Connie Marras 1
- 1The Edmond J. Safra Program in Parkinson's Disease, University Health Network, Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
- 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
- 3Mayo Clinic, Jacksonville, Florida.
- 4University of Pennsylvania, Philadelphia.
- 5Columbia University, New York, New York.
- 6Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain.
- 7Hospital Universitario Donostia, CIBERNED, San Sebastián, Spain.
- 8Bellvitge University Hospital, L' Hospitalet de Llobregat, Barcelona, Spain.
- 9Veterans Affairs Medical Center, San Francisco, California.
- 10The Parkinson's Institute, Sunnyvale, California.
- 11St Olavs Hospital, Trondheim, Norway.
- 12University of Turin, Turin, Italy.
- 13Erasmus MC, Rotterdam, the Netherlands.
- 14Skåne University Hospital and Lund University, Lund, Sweden.
- 15Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy.
- 16Centre Hospitalier Universitaire La Timone, Marseille, France.
- 17Sagamihara National Hospital, Kanagawa, Japan.
- 18Sorbonne Université, Pierre and Marie Curie University, Institut du Cerveau et de la Moelle Epinière, Institut National de la Santé et de la Recherche Médicale, Centre national de la recherche scientique, Paris, France.
- 19University of British Columbia, Vancouver, British Columbia, Canada.
- 0The Edmond J. Safra Program in Parkinson's Disease, University Health Network, Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
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View abstract on PubMed
Summary
This summary is machine-generated.Parkinson disease (PD) linked to LRRK2 mutations can present without Lewy bodies (LBs). The presence of LBs in LRRK2-PD correlates with cognitive impairment, while their absence suggests a motor-dominant phenotype.
Area Of Science
- Neuroscience
- Genetics
- Pathology
Background
- Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common genetic cause of Parkinson disease (PD).
- Clinical presentation of LRRK2-PD often resembles sporadic PD.
- Some LRRK2-PD cases lack Lewy bodies (LBs), a key neuropathological feature of PD.
Purpose Of The Study
- To investigate the correlation between the presence or absence of Lewy bodies (LBs) and clinical features in LRRK2-related Parkinson disease (PD).
Main Methods
- Analysis of genetic, clinical, and neuropathological data from 37 LRRK2-PD cases.
- Correlation of specific LRRK2 mutations (e.g., p.G2019S) with LB pathology.
- Comparison of clinical phenotypes based on LB presence or absence.
Main Results
- The LRRK2 p.G2019S mutation was most frequently associated with LB pathology.
- Non-motor features including cognitive impairment, dementia, anxiety, and orthostatic hypotension correlated with the presence of LBs.
- A predominantly motor phenotype was associated with the absence of LBs.
Conclusions
- Parkinsonian motor features can manifest in LRRK2-PD even without Lewy bodies (LBs).
- LB pathology in LRRK2-PD may indicate a more complex symptom profile, including cognitive deficits.
- This study provides novel clinicopathological correlations for LRRK2-related Parkinson disease.
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