TY - JOUR
T1 - Clinical correlations with lewy body pathology in LRRK2-related Parkinson disease
AU - Kalia, Lorraine V.
AU - Lang, Anthony E.
AU - Hazrati, Lili Naz
AU - Fujioka, Shinsuke
AU - Wszolek, Zbigniew K.
AU - Dickson, Dennis W.
AU - Ross, Owen A.
AU - Van Deerlin, Vivianna M.
AU - Trojanowski, John Q.
AU - Hurtig, Howard I.
AU - Alcalay, Roy N.
AU - Marder, Karen S.
AU - Clark, Lorraine N.
AU - Gaig, Carles
AU - Tolosa, Eduardo
AU - Ruiz-Martínez, Javier
AU - Marti-Masso, Jose F.
AU - Ferrer, Isidre
AU - López De Munain, Adolfo
AU - Goldman, Samuel M.
AU - Schüle, Birgitt
AU - Langston, J. William
AU - Aasly, Jan O.
AU - Giordana, Maria T.
AU - Bonifati, Vincenzo
AU - Puschmann, Andreas
AU - Canesi, Margherita
AU - Pezzoli, Gianni
AU - Maues De Paula, Andre
AU - Hasegawa, Kazuko
AU - Duyckaerts, Charles
AU - Brice, Alexis
AU - Stoessl, A. Jon
AU - Marras, Connie
N1 - Publisher Copyright:
Copyright 2014 American Medical Association. All rights reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013.Among the different mutations, the LRRK2 p.G2019S mutation was most frequently associated with LB pathology.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.
AB - 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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U2 - 10.1001/jamaneurol.2014.2704
DO - 10.1001/jamaneurol.2014.2704
M3 - Article
C2 - 25401511
AN - SCOPUS:84921033215
SN - 2168-6149
VL - 72
SP - 100
EP - 105
JO - JAMA neurology
JF - JAMA neurology
IS - 1
ER -