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JAMA Neurol. 2015 Jan;72(1):100-5. doi: 10.1001/jamaneurol.2014.2704.

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

Author information

1
The Edmond J. Safra Program in Parkinson's Disease, University Health Network, Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
2
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
3
Mayo Clinic, Jacksonville, Florida.
4
University of Pennsylvania, Philadelphia.
5
Columbia University, New York, New York.
6
Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain.
7
Hospital Universitario Donostia, CIBERNED, San Sebastián, Spain.
8
Bellvitge University Hospital, L' Hospitalet de Llobregat, Barcelona, Spain.
9
Veterans Affairs Medical Center, San Francisco, California.
10
The Parkinson's Institute, Sunnyvale, California.
11
St Olavs Hospital, Trondheim, Norway.
12
University of Turin, Turin, Italy.
13
Erasmus MC, Rotterdam, the Netherlands.
14
Skåne University Hospital and Lund University, Lund, Sweden.
15
Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy.
16
Centre Hospitalier Universitaire La Timone, Marseille, France.
17
Sagamihara National Hospital, Kanagawa, Japan.
18
Sorbonne 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.
19
University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

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describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013.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.

PMID:
25401511
PMCID:
PMC4399368
DOI:
10.1001/jamaneurol.2014.2704
[Indexed for MEDLINE]
Free PMC Article

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