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.

CONCLUSION:

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: Meghan C Campbell, Jonathan M Koller, Abraham Z Snyder, Chandana Buddhala, Paul T Kotzbauer, Joel S Perlmutter
• Journal: Neurology (Neurology) Vol. 84 Issue 24 Pg. 2413-21 (Jun 16 2015) ISSN: 1526-632X [Electronic] United States
• PMID: 25979701 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Academy of Neurology.

Chemical References

• 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
• Amyloid beta-Peptides
• Aniline Compounds
• Biomarkers
• Peptide Fragments
• Radiopharmaceuticals
• SNCA protein, human
• Thiazoles
• alpha-Synuclein
• amyloid beta-protein (1-42)

Topics

• Aged
• Aged, 80 and over
• Amyloid beta-Peptides (cerebrospinal fluid)
• Aniline Compounds
• Biomarkers (cerebrospinal fluid)
• Brain (diagnostic imaging, physiopathology)
• Brain Mapping
• Female
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Motor Activity
• Neural Pathways (diagnostic imaging, physiopathology)
• Parkinson Disease (cerebrospinal fluid, diagnostic imaging, physiopathology)
• Peptide Fragments (cerebrospinal fluid)
• Positron-Emission Tomography
• Radiopharmaceuticals
• Rest
• Severity of Illness Index
• Spinal Puncture
• Thiazoles
• alpha-Synuclein (cerebrospinal fluid)