title: CSF proteins and resting-state functional connectivity in Parkinson disease.
abstract: OBJECTIVE
  The purpose of this study was to investigate the relationship between disruption of MRI-measured resting-state functional connectivity (rs-fcMRI) brain networks and CSF levels of potentially pathogenic proteins that reflect brain pathology in Parkinson disease (PD).
  
  
  METHODS
  PD participants without dementia (n = 43) and age-matched controls (n = 22) had lumbar punctures to measure CSF protein levels, Pittsburgh compound B (PiB)-PET imaging, and rs-fcMRI while off medication. Imaging analyses focused on 5 major resting-state networks as well as the striatum.
  
  
  RESULTS
  Participants with PD had significantly reduced sensorimotor functional connectivity, which correlated with reduced CSF levels of α-synuclein. The PD group also had significantly stronger default mode network functional connectivity that did not correlate with CSF β-amyloid (Aβ)42 or PiB uptake. In contrast, default mode network functional connectivity in the control group did correlate with CSF Aβ42 levels. Functional connectivity was similar between groups in the dorsal attention, control, and salience networks.
  
  
  CONCLUSIONS
  These results suggest that abnormal α-synuclein accumulation, but not Aβ, contributes to the disruption of motor-related functional connectivity in PD. Furthermore, correlating CSF protein measures with the strength of resting-state networks provides a direct link between abnormal α-synuclein metabolism and disrupted brain function in PD.
authors.affiliation: From the Departments of Neurology (M.C.C., C.B., P.T.K., J.S.P.), Radiology (M.C.C., A.Z.S., J.S.P.), Psychiatry (J.M.K.), and Anatomy & Neurobiology (J.S.P.), and Programs in Occupational Therapy (J.S.P.) and Physical Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO. meghanc@npg.wustl.edu.
authors.forename: Meghan C
authors.initials: MC
authors.lastname: Campbell
authors.affiliation: From the Departments of Neurology (M.C.C., C.B., P.T.K., J.S.P.), Radiology (M.C.C., A.Z.S., J.S.P.), Psychiatry (J.M.K.), and Anatomy & Neurobiology (J.S.P.), and Programs in Occupational Therapy (J.S.P.) and Physical Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Koller
authors.affiliation: From the Departments of Neurology (M.C.C., C.B., P.T.K., J.S.P.), Radiology (M.C.C., A.Z.S., J.S.P.), Psychiatry (J.M.K.), and Anatomy & Neurobiology (J.S.P.), and Programs in Occupational Therapy (J.S.P.) and Physical Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.affiliation: From the Departments of Neurology (M.C.C., C.B., P.T.K., J.S.P.), Radiology (M.C.C., A.Z.S., J.S.P.), Psychiatry (J.M.K.), and Anatomy & Neurobiology (J.S.P.), and Programs in Occupational Therapy (J.S.P.) and Physical Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Chandana
authors.initials: C
authors.lastname: Buddhala
authors.affiliation: From the Departments of Neurology (M.C.C., C.B., P.T.K., J.S.P.), Radiology (M.C.C., A.Z.S., J.S.P.), Psychiatry (J.M.K.), and Anatomy & Neurobiology (J.S.P.), and Programs in Occupational Therapy (J.S.P.) and Physical Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Kotzbauer
authors.affiliation: From the Departments of Neurology (M.C.C., C.B., P.T.K., J.S.P.), Radiology (M.C.C., A.Z.S., J.S.P.), Psychiatry (J.M.K.), and Anatomy & Neurobiology (J.S.P.), and Programs in Occupational Therapy (J.S.P.) and Physical Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000814:Aniline Compounds; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012146:Rest; D012720:Severity of Illness Index; D013129:Spinal Puncture; D013844:Thiazoles; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; C497604:SNCA protein, human; D013844:Thiazoles; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42)