Abstract
Objective To evaluate the association of Alzheimer’s disease-related and inflammation-related cerebrospinal fluid (CSF) markers with freezing of gait (FOG) in patients with Parkinson’s disease (PD).
Method The study population included well-characterized PD patients with FOG (PD-FOG), without FOG (PD-NoFOG) and healthy controls (HC). CSF was collected using standard protocols. Three Alzheimer’s disease-related markers and 10 inflammation-related markers were measured in a Luminex 200 platform. Differences in marker expression across groups were evaluated with multivariate linear models.
Results CSF was collected from PD-FOG (N=12), PD-NoFOG (N=20) and HC (N=11) for analysis. Age was not significantly different between the three groups. Duration of PD was not significantly different between the two PD groups. After adjusting for covariates and multiple comparisons, the anti-inflammatory marker, fractalkine, was significantly decreased in the PD groups compared to HC (P=0.022), and further decreased in PD-FOG compared to PD-NoFOG or HC (P=0.032). The Alzheimer’s disease-related protein, Aβ42, was increased in PD-FOG compared to PD-NoFOG or HC (P=0.004). p-Tau181 was also decreased in both PD groups compared to HC (P=0.010).
Conclusions We found high levels of Aβ42 in PD-FOG patients and cross-sectional data which supports an increase over time from early to advanced state. We also found low levels of fractalkine which might suggest anti-inflammatory effect. This is the first time an association between fractalkine and FOG has been shown. Whether these changes are specific to FOG requires further exploration.
Competing Interest Statement
The authors have declared no competing interest.
Clinical Trial
This was an observational cross sectional study and therefore it was not registered.
Funding Statement
Curtis Family Fund, Sartain Lanier Family Foundation, Parkinson Foundation, NIH K25HD086276 (JLM), Parkinsons Foundation Fellowship
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
All protocols were approved by the Emory University Institutional Review Board
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Footnotes
Funding: William N. and Bernice E. Bumpus Foundation, Curtis family Fund; Sartain Lanier Family Foundation; American Parkinson’s Disease Association; NIH K25 HD086276
Statistical analysis was completed by J. Lucas McKay, Ph.D., M.S.C.R. from Emory University.
Study Funding: Curtis Family Fund, Sartain Lanier Family Foundation (SAF), Parkinson Foundation, NIH K25HD086276 (JLM), Parkinson’s Foundation Fellowship (SPP)
Disclosures:
Dr. Hatcher-Martin has the following disclosures:
Honoraria: Acadia, Neurocrine, Parkinson’s Foundation
Dr. McKay has the following disclosures:
Consulting fees: Biocircuit Technologies.
Mr. Howell has nothing to disclose.
Dr. Goldstein reports no disclosures.
Dr. Hu has patent or patent-pending on CSF diagnosis of FTLD-TDP, CSF prognosis of SMA, and serological assays for COVID-19; licensed serological assays for COVID-19 to Sigma- Millipore; consulted for Biogen Inc., Fujirebio Diagnostics Inc., Apellis Pharmaceuticals, and AARP; and received research support from Fujirebio Diagnostics Inc.
Dr. Factor has the following disclosures:
Honoraria: Lundbeck, Teva, Sunovion, Biogen, Acadia, Neuroderm, Acorda, CereSpire.
Grants: Ipsen, Medtronic, Boston Scientific, Teva, US World Meds, Sunovion Therapeutics, Vaccinex, Voyager, Jazz Pharmaceuticals, Lilly, CHDI Foundation, Michael J. Fox Foundation, Royalties: Demos, Blackwell Futura for textbooks, Uptodate
Other Bracket Global LLC, CNS Ratings LLC
Authors roles:
JM Hatcher-Martin: Co-first author, Research Project- Conception, Organization, Execution, Statistical analysis-review and critique, Manuscript: Review and critique, Arranged funding JL McKay: Co-first author, Research Project-Execution, Statistical analysis-Execution, Manuscript: Writing of the first draft, review and critique
B Sommerfeld: Research Project-Execution, Statistical analysis- no role, Manuscript: Review and Critique
JC Howell: Research Project-Execution, Statistical analysis- no role, Manuscript: Review and Critique
FC Goldstein: Research Project-Execution, Statistical analysis- Review and Critique, Manuscript: Review and Critique
WT Hu: Research Project-Execution, Statistical analysis- Review and Critique, Manuscript: Review and Critique
SA Factor: Research project: Conception, Organization, Execution, Statistical Analysis: Review and Critique; Manuscript: Writing of the first draft, Arranged funding
Data Availability
Data not available in this manuscript will be shared at the request of other qualified investigators for purposes of replicating procedures and results.
