Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease

IMPORTANCE: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associ...

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Detalles Bibliográficos
Autores: Kalia, Lorraine V., Lang, Anthony E., Hazrati, Lili-Naz, Fujioka, Shinsuke, Wszolek, Zbigniew K., Dickson, Dennis W., Ross, Owen A., Van Deerlin, Vivianna M., Trojanowski, John Q., Hurtig, Howard I., Alcalay, Roy N., Marder, Karen S., Clark, Lorraine N., Gaig Ventura, Carles, Tolosa, Eduardo, Ruiz-Martínez, Javier, Marti-Masso, Jose F., Ferrer, Isidro (Ferrer Abizanda), López de Munain, Adolfo, Goldman, Samuel M., Schüle, Birgitt, Langston, J. William, Aasly, Jan O., Giordana, Maria T., Bonifati, Vincenzo, Puschmann, Andreas, Canesi, Margherita, Pezzoli, Gianni, Maues De Paula, Andre, Hasegawa, Kazuko, Duyckaerts, Charles, Brice, Alexis, Stoessl, A. Jon, Marras, Connie
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/141944
Acceso en línea:https://hdl.handle.net/2445/141944
Access Level:acceso abierto
Palabra clave:Demència amb cossos de Lewy
Patologia
Mutació (Biologia)
Malaltia de Parkinson
Genètica
Lewy body dementia
Pathology
Mutation (Biology)
Parkinson's disease
Genetics
Descripción
Sumario:IMPORTANCE: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD. OBSERVATIONS: We describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013. Among the different mutations, the LRRK2 p.G2019S mutation was most frequently associated with LB pathology. Nonmotor features of cognitive impairment/dementia, anxiety, and orthostatic hypotension were correlated with the presence of LBs. In contrast, a primarily motor phenotype was associated with a lack of LBs. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first report of clinicopathological correlations in a series of LRRK2-related PD cases. Findings from this selected group of patients with PD demonstrated that parkinsonian motor features can occur in the absence of LBs. However, LB pathology in LRRK2-related PD may be a marker for a broader parkinsonian symptom complex including cognitive impairment.

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