Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers

J. O. Aasly, M. Shi, V. Sossi, T. Stewart, K. K. Johansen, Zbigniew K Wszolek, R. J. Uitti, K. Hasegawa, T. Yokoyama, C. P. Zabetian, H. M. Kim, J. B. Leverenz, C. Ginghina, J. Armaly, K. L. Edwards, K. W. Snapinn, A. J. Stoessl, J. Zhang

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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.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalNeurology
Volume78
Issue number1
DOIs
StatePublished - Jan 3 2012

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Amyloid
Parkinson Disease
Cerebrospinal Fluid
Mutation
Levodopa
Corpus Striatum
Asymptomatic Diseases
Methylphenidate
Positron-Emission Tomography
Parkinson's Disease
Carrier
Biomarkers
Phenotype
Proteins

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Aasly, J. O., Shi, M., Sossi, V., Stewart, T., Johansen, K. K., Wszolek, Z. K., ... Zhang, J. (2012). Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers. Neurology, 78(1), 55-61. https://doi.org/10.1212/WNL.0b013e31823ed101

Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers. / Aasly, J. O.; Shi, M.; Sossi, V.; Stewart, T.; Johansen, K. K.; Wszolek, Zbigniew K; Uitti, R. J.; Hasegawa, K.; Yokoyama, T.; Zabetian, C. P.; Kim, H. M.; Leverenz, J. B.; Ginghina, C.; Armaly, J.; Edwards, K. L.; Snapinn, K. W.; Stoessl, A. J.; Zhang, J.

In: Neurology, Vol. 78, No. 1, 03.01.2012, p. 55-61.

Research output: Contribution to journalArticle

Aasly, JO, Shi, M, Sossi, V, Stewart, T, Johansen, KK, Wszolek, ZK, Uitti, RJ, Hasegawa, K, Yokoyama, T, Zabetian, CP, Kim, HM, Leverenz, JB, Ginghina, C, Armaly, J, Edwards, KL, Snapinn, KW, Stoessl, AJ & Zhang, J 2012, 'Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers', Neurology, vol. 78, no. 1, pp. 55-61. https://doi.org/10.1212/WNL.0b013e31823ed101
Aasly, J. O. ; Shi, M. ; Sossi, V. ; Stewart, T. ; Johansen, K. K. ; Wszolek, Zbigniew K ; Uitti, R. J. ; Hasegawa, K. ; Yokoyama, T. ; Zabetian, C. P. ; Kim, H. M. ; Leverenz, J. B. ; Ginghina, C. ; Armaly, J. ; Edwards, K. L. ; Snapinn, K. W. ; Stoessl, A. J. ; Zhang, J. / Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers. In: Neurology. 2012 ; Vol. 78, No. 1. pp. 55-61.
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T1 - Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers

AU - Aasly, J. O.

AU - Shi, M.

AU - Sossi, V.

AU - Stewart, T.

AU - Johansen, K. K.

AU - Wszolek, Zbigniew K

AU - Uitti, R. J.

AU - Hasegawa, K.

AU - Yokoyama, T.

AU - Zabetian, C. P.

AU - Kim, H. M.

AU - Leverenz, J. B.

AU - Ginghina, C.

AU - Armaly, J.

AU - Edwards, K. L.

AU - Snapinn, K. W.

AU - Stoessl, A. J.

AU - Zhang, J.

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N2 - 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.

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