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Decrease in Aβ42 predicts dopa-resistant gait progression in early Parkinson disease.

Lynn Rochester1, Brook Galna2, Sue Lord2

  • 1From the Institute of Neuroscience (L.R., B.G., S.L., A.J.Y., R.M., G.D., T.K.K., D.J.B.), Clinical Ageing Research Unit, Newcastle University; Department of Geriatric Medicine (G.D.), University of Edinburgh, UK; School of Medicine & Menzies Health Institute (T.K.K.), Griffith University, Australia; and Paracelsus-Elena Klinik, Kassel and University Medical Centre (Institute of Neuropathology and Department of Neurosurgery) (B.M.), Göttingen, Germany. lynn.rochester@ncl.ac.uk.

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Summary
This summary is machine-generated.

Low levels of cerebrospinal fluid amyloid-beta biomarkers predict worsening gait in early Parkinson disease (PD). This suggests amyloid pathology may contribute to motor symptoms, offering potential therapeutic targets for gait disturbances.

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Area of Science:

  • Neuroscience
  • Neurology
  • Biomarker Research

Background:

  • Parkinson disease (PD) is characterized by motor symptoms, including gait impairments.
  • Dopa-resistant gait impairments represent a significant challenge in PD management.
  • The role of cerebrospinal fluid (CSF) biomarkers in predicting PD progression is an active area of research.

Purpose of the Study:

  • To investigate the predictive value of CSF biomarkers for the progression of dopa-resistant gait impairments in early Parkinson disease.
  • To examine the association between specific CSF biomarkers (amyloid-beta, tau, alpha-synuclein) and gait characteristics over the first 36 months post-diagnosis.

Main Methods:

  • Prospective observational study involving 108 individuals with PD and 130 controls.
  • Longitudinal quantitative gait analysis using an instrumented walkway (GAITRite).
  • Measurement of CSF biomarkers: Aβ42, Aβ40, t-tau, p-tau181, and αSyn in a subgroup of 44 PD patients.
  • Statistical analysis using linear mixed models to assess the relationship between CSF biomarkers and gait parameters.

Main Results:

  • Low baseline levels of CSF Aβ42, and to a lesser extent Aβ40, significantly predicted the decline in gait characteristics within the first three years of PD diagnosis.
  • These amyloid-beta biomarkers independently explained up to 12% of the progression in step time variability (single-task) and step length variability (dual-task).
  • The predictive association remained significant regardless of patient age and cognitive status.

Conclusions:

  • The findings suggest that underlying amyloid pathology plays a role in the neural networks controlling locomotor function in PD.
  • Disturbed amyloid-beta metabolism may serve as a potential biomarker for identifying individuals at higher risk of developing dopa-resistant gait impairments in early PD.
  • These results open avenues for therapeutic strategies targeting amyloid burden to alleviate gait disturbances and potentially reduce fall risk in early PD patients.