@article{13d398ec1cd84c5a86a0f81a9ab2bc0b,
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.",
author = "Aasly, {J. O.} and M. Shi and V. Sossi and T. Stewart and Johansen, {K. K.} and Wszolek, {Z. K.} and Uitti, {R. J.} and K. Hasegawa and T. Yokoyama and Zabetian, {C. P.} and Kim, {H. M.} and Leverenz, {J. B.} and C. Ginghina and J. Armaly and Edwards, {K. L.} and Snapinn, {K. W.} and Stoessl, {A. J.} and J. Zhang",
note = "Funding Information: Dr. Aasly serves on tzhe editorial boards of Parkinsonism and Related Disorders, Parkinson's Disease , and the Journal of the Norwegian Medical Association ; and his institution receives annual royalties from Lundbeck Inc. from the licensing of the technology related to PARK8/LRRK2. Dr. Shi reports no disclosures. Dr. Sossi has received research support from Pacific Alzheimer Research Foundation. Dr. Stewart and Dr. Johansen report no disclosures. Dr. Wszolek serves as Co-Editor-in-Chief of Parkinsonism and Related Disorders , Regional Editor of the European Journal of Neurology , and on the editorial boards of Neurologia i Neurochirurgia Polska, Advances in Rehabilitation , the Medical Journal of the Rzeszow University , and Clinical and Experimental Medical Letters ; holds and has contractual rights for receipt of future royalty payments from patents re: A novel polynucleotide involved in heritable Parkinson's disease; receives royalties from publishing Parkinsonism and Related Disorders (Elsevier, 2007, 2008, 2009) and the European Journal of Neurology (Wiley-Blackwell, 2007, 2008, 2009); and receives research support from Allergan, Inc., the NIH/NINDS, Mayo Clinic Florida Research Committee CR program, the Pacific Alzheimer Research Foundation (Canada), the CIHR, the Mayo Clinic Florida Research Committee CR program, and a gift from Carl Edward Bolch, Jr., and Susan Bass Bolch. Dr. Uitti serves as an Associate Editor of Neurology {\textregistered}; has received research support from Advanced Neuromodulations Systems and from the NIH; and his institution receives annual royalties from Lundbeck Inc. from the licensing of the technology related to PARK8/LRRK2. Dr. Hasegawa and Dr. Yokoyama report no disclosures. Dr. Zabetian has received research support from NIH (NINDS/NIA), the US Department of Veterans Affairs, the Parkinson's Disease Foundation, and the American Parkinson Disease Association. Dr. Kim reports no disclosures. Dr. Leverenz has served as a consultant for Bayer Schering Pharma, Novartis, and Teva Pharmaceutical Industries Ltd.; has received speaker honoraria from Novartis; and receives research support from the NIH/NIND, the Michael J. Fox Foundation, the Washington Chapter American Parkinson's Disease Association/Northwest Collaborative Care, and the US Department of Veterans Affairs. Dr. Ginghina and J. Armaly report no disclosures. Dr. Edwards has received research support from the NIH and the Centers for Disease Control. K.W. Snapinn has received research support from the NIH, the US Department of Veterans Affairs, and the Centers for Disease Control. Dr. Stoessl serves on a scientific advisory board for Biovail Corporation/Medgenesis; has received funding for travel and speaker honoraria from Novartis, Teva Pharmaceutical Industries Ltd., Allergan, Inc., and Abbott; serves on the editorial boards of Annals of Neurology, Lancet Neurology , and Parkinsonism & Related Disorders ; and receives research support from CIHR, the Michael Smith Foundation for Health Research, the Michael J. Fox Foundation, and the Pacific Alzheimer Research Foundation. Dr. Zhang serves on the editorial boards of Neurological Disease, Neurochemical Research , the Journal of Alzheimer's Disease , and Proteomics ; and has received research support from the NIH. Funding Information: Supported by NIH (AG025327, AG033398, P30ES007033-6364, ES004696-5897, ES012703, ES016873, NS057567, NS060252 to J.Z., P50NS062684 to C.P.Z., J.B.L., and J.Z., NS065070 to C.P.Z., NS057567 and P50NS072187 to Z.K.W. and R.J.U.), Department of Veterans Affairs (to J.B.L. and H.M.K., and 1I01BX000531 to C.P.Z.), Canadian Institutes of Health Research (to A.J.S.), Michael Smith Foundation for Health Research (to A.J.S.), Pacific Alzheimer Research Foundation (to A.J.S.), Canada Research Chairs program (to A.J.S.), TRIUMF (to A.J.S.), Mayo Clinic Florida Research Committee CR program (to Z.K.W. and R.J.U.), the gift from Carl Edward Bolch, Jr. and Susan Bass Bolch (to Z.K.W. and R.J.U.), and Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labour and Welfare of Japan (to K.H. and T.Y.). ",
year = "2012",
month = jan,
day = "3",
doi = "10.1212/WNL.0b013e31823ed101",
language = "English (US)",
volume = "78",
pages = "55--61",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "1",
}