title: Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers.
abstract: OBJECTIVE
  The goal of the current investigation was to examine a cohort of symptomatic and asymptomatic LRRK2 mutation carriers, in order to address whether the reported alterations in amyloid β (Aβ) and tau species in the CSF of patients with sporadic Parkinson disease (PD) are a part of PD pathogenesis, the aging process, or a comorbid disease in patients with PD, and to explore the possibility of Aβ and tau as markers of early or presymptomatic PD.
  
  
  METHODS
  CSF Aβ42, total tau, and phosphorylated tau were measured with Luminex assays in 26 LRRK2 mutation carriers, who were either asymptomatic (n = 18) or had a phenotype resembling sporadic PD (n = 8). All patients also underwent PET scans with 18F-6-fluoro-l-dopa (FD), 11C-(±)-α-dihydrotetrabenazine (DTBZ), and 11C-d-threo-methylphenidate (MP) to measure dopaminergic function in the striatum. The levels of CSF markers were then compared to each PET measurement.
  
  
  RESULTS
  Reduced CSF Aβ42 and tau levels correlated with lower striatal dopaminergic function as determined by all 3 PET tracers, with a significant association between Aβ42 and FD uptake. When cases were restricted to carriers of the G2019S mutation, the most common LRRK2 variant in our cohort, significant correlations were also observed for tau.
  
  
  CONCLUSIONS
  The disposition of Aβ and tau is likely important in both LRRK2-related and sporadic PD, even during early phases of the disease. A better understanding of their production, aggregation, and degradation, including changes in their CSF levels, may provide insights into the pathogenesis of PD and the potential utility of these proteins as biomarkers.
authors.affiliation: Department of Neurology, St. Olav’s University Hospital, Trondheim, Norway.
authors.forename: J O
authors.initials: JO
authors.lastname: Aasly
authors.forename: M
authors.initials: M
authors.lastname: Shi
authors.forename: V
authors.initials: V
authors.lastname: Sossi
authors.forename: T
authors.initials: T
authors.lastname: Stewart
authors.forename: K K
authors.initials: KK
authors.lastname: Johansen
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: R J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: C P
authors.initials: CP
authors.lastname: Zabetian
authors.forename: H M
authors.initials: HM
authors.lastname: Kim
authors.forename: J B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: C
authors.initials: C
authors.lastname: Ginghina
authors.forename: J
authors.initials: J
authors.lastname: Armaly
authors.forename: K L
authors.initials: KL
authors.lastname: Edwards
authors.forename: K W
authors.initials: KW
authors.lastname: Snapinn
authors.forename: A J
authors.initials: AJ
authors.lastname: Stoessl
authors.forename: J
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000235:genetics; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases