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NEUROLOGY 2008;71:1021-1026
© 2008 American Academy of Neurology

Hyposmia in G2019S LRRK2-related parkinsonism

Clinical and pathologic data L. Silveira-Moriyama, MD, L. C. Guedes, MD, A. Kingsbury, PhD, H. Ayling, MSc, K. Shaw, RMN, E. R. Barbosa, MD, V. Bonifati, MD, PhD, N. P. Quinn, MD, P. Abou-Sleiman, PhD, N. W. Wood, PhD, A. Petrie, MSc, CStat, C. Sampaio, MD, PhD, J. J. Ferreira, MD, J. Holton, PhD, T. Revesz, MD and A. J. Lees, MD

From the Reta Lila Weston Institute of Neurological Studies (L.S.-M., A.K., J.H., T.R., A.J.L.), Queen Square Brain Bank (H.A., K.S., J.H., T.R., A.J.L.), Sobell Department of Motor Neuroscience and Movement Disorders (N.P.Q.), and Department of Molecular Neuroscience (P.A.-S., N.W.W.), UCL Institute of Neurology, London, UK; Neurological Clinical Research Unit (L.C.G., C.S., J.J.F.), Institute of Molecular Medicine, Lisbon, Portugal; Neurology Department (E.R.B.), Sao Paulo School of Medicine, Brazil; Department of Clinical Genetics (V.B.), Erasmus MC, Rotterdam, The Netherlands; and Biostatistics Unit (A.P.), UCL Eastman Dental Institute, London, UK.

Address correspondence and reprint requests to Prof. Andrew Lees, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, 1 Wakefield St, London, WC1N 1PJ, UK alees{at}ion.ucl.ac.uk

Background: Mutations in PARK8 (LRRK2) are associated with autosomal dominant parkinsonism and Parkinson disease (PD). Hyposmia is present in at least 80% of patients with PD and an accumulation of {alpha}-synuclein ({alpha}-syn) is seen in the olfactory pathways. In this study we have clinically examined olfaction and pathologically examined the rhinencephalon in individuals carrying the G2019S LRRK2 mutation.

Methods: The University of Pennsylvania Smell Test (UPSIT) was used to evaluate the sense of smell in 19 parkinsonian and two asymptomatic carriers of the G2019S mutation and compared with groups of patients with PD and healthy controls. Postmortem examination of {alpha}-syn accumulation in the rhinencephalon was also carried out in four parkinsonian carriers of the G2019S mutation.

Results: The mean UPSIT score in G2019S parkinsonian carriers was lower than that in healthy controls (p < 0.001) and similar to that found in patients with PD (p > 0.999). Smell tests in two asymptomatic carriers of the G2019S mutation were in the normal range. Postmortem studies of the olfactory pathways in one of the patients who had been clinically tested, and found to have hyposmia, and three other cases with the G2019S mutation, revealed {alpha}-syn deposition in the olfactory pathways in all cases.

Conclusions: Odor identification is diminished in LRRK2 G2019S mutation parkinsonism but the asymptomatic carriers of the mutation had normal olfaction. We found {alpha}-syn accumulation with Lewy bodies in the rhinencephalon in all four cases examined pathologically.

Abbreviations: {alpha}-syn = {alpha}-synuclein; AOI = area of interest; CERAD = Consortium to Establish a Registry for Alzheimer’s Disease; LB = Lewy body; OT = olfactory tract; PD = Parkinson disease; QSBB = Queen Square Brain Bank for Neurological Disorders; UPSIT = University of Pennsylvania Smell Test.

Supplemental data at www.neurology.org

Disclosure: The authors report no disclosures.

Received January 16, 2008. Accepted in final form May 21, 2008.