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Lookup NU author(s): Professor David BrooksORCiD,
Professor Nicola PaveseORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by National Academy of Sciences, 2021.
For re-use rights please refer to the publisher's terms and conditions.
Synucleinopathies are neurodegenerative diseases with both central and peripheral immune responses. However, whether the peripheral immune changes occur early in disease and their relation to brain events is yet unclear. Isolated rapid-eye-movement sleep behaviour disorder (iRBD) can precede synucleinopathy-related parkinsonism and provides a prodromal phenotype to study early Parkinson's disease events. In this prospective case-control study, we describe monocytic markers in a cohort of iRBD patients that were associated with the brain imaging markers of inflammation and neuronal dysfunction. Using 11C-PK11195 positron emission tomography (PET), we previously showed increased immune activation in the substantia nigra of iRBD patients, while 18F-DOPA positron emission tomography detected reduced putaminal dopaminergic function. Here we describe that patients’ blood monocytic cells showed increased expression of CD11b, while HLA-DR expression was decreased compared to healthy controls. The iRBD patients had increased classical monocytes and mature natural killer cells. Remarkably, the levels of expression of TLR4 on blood monocytes in iRBD patients were positively correlated with nigral immune activation measured by 11C-PK11195 PET and negatively correlated with putaminal 18F-DOPA uptake; - the opposite was seen for the percentage of CD163+ myeloid cells. This suggests a deleterious role for TLR4 and, conversely, a protective one for the CD163 expression. We show, for the first time, an association between peripheral blood monocytes and brain immune and dopaminergic changes in a synucleinopathy related disorder, thus suggesting a cross-talk between periphery and brain during the disease.
Author(s): Farmen K, Nissen SK, Stokholm MG, Iranzo A, Østergaard K, Serradell M, Otto M, Svendsen KB, Garrido A, Vilas D, Borghammer P, Santamaria J, Møller A, Gaig C, Brooks DJ, Tolosa E, Pavese N, Romero-Ramos M
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences of the United States of America
Print publication date: 09/03/2021
Online publication date: 09/03/2021
Acceptance date: 28/01/2021
Date deposited: 01/02/2021
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
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