title: Olfaction and imaging biomarkers in premotor LRRK2 G2019S-associated Parkinson disease.
abstract: OBJECTIVE
  To ascertain in a cross-sectional study whether substantia nigra (SN) echogenicity, olfaction, and dopamine transporter (DaT)-SPECT are reliable premotor biomarkers in a cohort of asymptomatic carriers of the LRRK2 G2019S mutation (AsG2019S+).
  
  
  METHODS
  These biomarkers were evaluated in 49 AsG2019S+ patients, and we also studied olfaction and SN echogenicity in 29 patients with G2019S-associated Parkinson disease (PD-G2019S), 47 relatives who were noncarriers of the LRRK2 G2019S mutation (AsG2019S-), 50 patients with idiopathic Parkinson disease (iPD), and 50 community controls.
  
  
  RESULTS
  Eighty-five percent of unaffected mutation carriers (AsG2019S+) showed pathologic SN hyperechogenicity, with a similar proportion observed among both PD-G2019S and iPD cases, and 41% of AsG2019S- also showing increased SN echogenicity. The proportion of hyposmic individuals was not statistically different in patients with PD-G2019S (50%) and iPD (82%), but hyposmia was significantly less common in both AsG2019S+ (26%) and AsG2019S- (28%). In AsG2019S+ cases, reduced striatal uptake in DaT-SPECT was observed in 43.7%.
  
  
  CONCLUSIONS
  Independently of age at examination, the most frequently altered premotor biomarker in LRRK2 G2019S-associated PD was SN hyperechogenicity, whereas abnormal DaT-SPECT predominated in older, unaffected mutation carriers.
authors: Neurology Service, Universitary Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Spain.
authors: Maria
authors: M
authors: Sierra
authors: Pascual
authors: P
authors: Sánchez-Juan
authors: María Isabel
authors: MI
authors: Martínez-Rodríguez
authors: Isabel
authors: I
authors: González-Aramburu
authors: Inés
authors: I
authors: García-Gorostiaga
authors: María Remedios
authors: MR
authors: Quirce
authors: Enrique
authors: E
authors: Palacio
authors: José Manuel
authors: JM
authors: Carril
authors: José
authors: J
authors: Berciano
authors: Onofre
authors: O
authors: Combarros
authors: Jon
authors: J
authors: Infante
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009662:Nortropanes / Q000493:pharmacokinetics; D000857:Olfaction Disorders / Q000000981:diagnostic imaging / Q000209:etiology*; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics; D012720:Severity of Illness Index; D012903:Smell / Q000235:genetics; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000473:pathology; D015899:Tomography, Emission-Computed, Single-Photon; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D015415:Biomarkers; D009662:Nortropanes; D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine; C519528:ioflupane