title: Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson's disease.
abstract: Individuals with Parkinson's disease (PD) often suffer from comorbid depression. P11 (S100A10), a member of the S100 family of proteins, is expressed widely throughout the body and is involved in major depressive disorder and antidepressant response. Central p11 levels are reduced in postmortem tissue from depressed individuals; however, p11 has not yet been investigated in PD patients with depression or those without depression. We investigated p11 levels in postmortem PD brains and assessed whether peripheral p11 levels correlate with disease severity. Substantia nigra, putamen, and cortical p11 protein levels were assessed in postmortem brain samples from PD patients and matched controls. In a different set of postmortem brains, p11 mRNA expression was measured in dopaminergic cells from the substantia nigra. Both p11 protein and mRNA levels were decreased in PD patients. Peripheral p11 protein levels were investigated in distinct leukocyte populations from PD patients with depression and those without depression. Monocyte, natural killer (NK) cell, and cytotoxic T-cell p11 levels were positively associated with the severity of PD, and NK cell p11 levels were positively associated with depression scores. Given that inflammation plays a role in both PD and depression, it is intriguing that peripheral p11 levels are altered in immune cells in both conditions. Our data provide insight into the pathological alterations occurring centrally and peripherally in PD. Moreover, if replicated in other cohorts, p11 could be an easily accessible biomarker for monitoring the severity of PD, especially in the context of comorbid depression.
authors.affiliation: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, SE-171 76 Stockholm, Sweden; Holly.green@ki.se greengard@mail.rockefeller.edu Per.Svenningsson@ki.se.
authors.forename: Holly
authors.initials: H
authors.lastname: Green
authors.affiliation: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, SE-171 76 Stockholm, Sweden.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Ludwig Institute for Cancer Research, SE-171 77 Stockholm, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Tiklova
authors.affiliation: Ludwig Institute for Cancer Research, SE-171 77 Stockholm, Sweden.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Volakakis
authors.affiliation: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, SE-171 76 Stockholm, Sweden.
authors.forename: Lovisa
authors.initials: L
authors.lastname: Brodin
authors.affiliation: Department of Medicine, Karolinska Institute, SE-171 76 Stockholm, Sweden.|Rheumatology Unit, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Berg
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; Holly.green@ki.se greengard@mail.rockefeller.edu Per.Svenningsson@ki.se.
authors.forename: Paul
authors.identifier: 0000-0002-4437-0893
authors.initials: P
authors.lastname: Greengard
authors.affiliation: Ludwig Institute for Cancer Research, SE-171 77 Stockholm, Sweden.|Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Perlmann
authors.affiliation: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, SE-171 76 Stockholm, Sweden; Holly.green@ki.se greengard@mail.rockefeller.edu Per.Svenningsson@ki.se.
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000097:blood / Q000235:genetics*; D001344:Autopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003865:Major Depressive Disorder / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D010300:Parkinson Disease / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D009418:S100 Proteins / Q000097:blood / Q000235:genetics*; D012720:Severity of Illness Index; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D000099248:S100 Calcium Binding Protein A10
chemical_list: D017306:Annexin A2; D012333:RNA, Messenger; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10
keywords: Parkinson's disease; S100A10; annexin II light chain; biomarker; depression