Colonic Alpha-Synuclein as Potential Early Biomarker for Parkinson's Disease Dementia

Document Type : Letter to the Editor

Author

Faculty of Medicine, University Indonesia, Jakarta, Indonesia

Abstract

Parkinson's Disease Dementia (PDD) is a cognitive and reasoning decline in many patients living with Parkinson's disease at least a year following diagnosis. PDD must be detected and treated promptly, as its advancement might impair the patient's quality of life. Alpha-synuclein deteriorates and extends to the limbic and neocortical regions in PDD, resulting in cognitive deficits. This development from PD to PDD may be associated with the quantity of aggregated alpha-synuclein in the colon. This also suggests employing the colonic alpha-synuclein cut-off concentration to detect the early progression of PD to PDD. Apart from concentration, the conformation of colonic alpha-synuclein can serve as a pathological hallmark. Despite the theoretical promise of colonic alpha-synuclein as an early diagnostic of PDD, the tissue sampling process may be a constraint. These restrictions, however, may be overcome with recent advancements in colonic biopsy technology. Thus, additional study is needed to close the information gap regarding using this biomarker as a possible early biomarker.

Keywords


  1. Aarsland D, Andersen K, Larsen JP, Lolk A. Prevalence and Characteristics of Dementia in Parkinson Disease: An 8-Year Prospective Study. Archives of Neurology. 2003;60(3):387-92.
  2. Schaeffer E, Kluge A, Böttner M, Zunke F, Cossais F, Berg D, et al. Alpha Synuclein Connects the Gut- Brain Axis in Parkinson’s Disease Patients - A View on Clinical Aspects, Cellular Pathology and Analytical Methodology. Front Cell Dev Biol. 2020;8:573696.
  3. Van der Perren A, Gelders G, Fenyi A, Bousset L, Brito F, Peelaerts W, et al. The structural differences between patient-derived α-synuclein strains dictate characteristics of Parkinson’s disease, multiple system atrophy and dementia with Lewy
    bodies. Acta Neuropathologica. 2020;139(6):977-1000.
  4. Poggiolini I, Gupta V, Lawton M, Lee S, El-Turabi A, Querejeta-Coma A, et al. Diagnostic value of cerebrospinal f luid alpha-synuclein seed quantification in synucleinopathies. Brain. 2022;145(2):584-95.