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Profiling the autoantibody repertoire reveals autoantibodies associated with mild cognitive impairment and dementia

journal contribution
submitted on 2024-08-26, 05:30 and posted on 2024-08-26, 05:31 authored by Hanan Ehtewish, Areej Mesleh, Georgios Ponirakis, Katie Lennard, Hanadi Al Hamad, Mani Chandran, Aijaz Parray, Houari Abdesselem, Patrick Wijten, Julie Decock, Nehad M. Alajez, Marwan Ramadan, Shafi Khan, Raheem Ayadathil, Ahmed Own, Ahmed Elsotouhy, Omar Albagha, Abdelilah Arredouani, Jonathan M. Blackburn, Rayaz A. Malik, Omar M. A. El-Agnaf

Background

Dementia is a debilitating neurological disease affecting millions of people worldwide. The exact mechanisms underlying the initiation and progression of the disease remain to be fully defined. There is an increasing body of evidence for the role of immune dysregulation in the pathogenesis of dementia, where blood-borne autoimmune antibodies have been studied as potential markers associated with pathological mechanisms of dementia.

Methods

This study included plasma from 50 cognitively normal individuals, 55 subjects with MCI (mild cognitive impairment), and 22 subjects with dementia. Autoantibody profiling for more than 1,600 antigens was performed using a high throughput microarray platform to identify differentially expressed autoantibodies in MCI and dementia.

Results

The differential expression analysis identified 33 significantly altered autoantibodies in the plasma of patients with dementia compared to cognitively normal subjects, and 38 significantly altered autoantibodies in the plasma of patients with dementia compared to subjects with MCI. And 20 proteins had significantly altered autoantibody responses in MCI compared to cognitively normal individuals. Five autoantibodies were commonly dysregulated in both dementia and MCI, including anti-CAMK2A, CKS1B, ETS2, MAP4, and NUDT2. Plasma levels of anti-ODF3, E6, S100P, and ARHGDIG correlated negatively with the cognitive performance scores (MoCA) (r2 –0.56 to −0.42, value of p < 0.001). Additionally, several proteins targeted by autoantibodies dysregulated in dementia were significantly enriched in the neurotrophin signaling pathway, axon guidance, cholinergic synapse, long-term potentiation, apoptosis, glycolysis and gluconeogenesis.

Conclusion

We have shown multiple dysregulated autoantibodies in the plasma of subjects with MCI and dementia. The corresponding proteins for these autoantibodies are involved in neurodegenerative pathways, suggesting a potential impact of autoimmunity on the etiology of dementia and the possible benefit for future therapeutic approaches. Further investigations are warranted to validate our findings.

Other Information

Published in: Frontiers in Neurology
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3389/fneur.2023.1256745

Funding

Qatar National Research Fund (NPRP12S-0213-190080), Corneal Confocal Microscopy: A rapid diagnostic and prognostic imaging biomarker for neurodegeneration in dementia.

Qatar Biomedical Research Institute (IDRP-2018-002).

History

Language

  • English

Publisher

Frontiers

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Qatar Biomedical Research Institute - HBKU
  • Neurological Disorders Research Center - QBRI
  • Diabetes Research Center - QBRI
  • Cancer Research Center - QBRI
  • Hamad Medical Corporation
  • Hamad General Hospital - HMC
  • Rumailah Hospital - HMC
  • Weill Cornell Medicine - Qatar

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