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Re-thinking the Etiological Framework of Neurodegeneration.

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Innovative research proposes four new views on neurodegenerative disease origins, focusing on cardiovascular, cellular senescence, trophic interactions, and gut-brain axis dysbiosis for better prevention and treatment.

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Area of Science:

  • Neuroscience
  • Pathology
  • Cardiovascular Science

Background:

  • Neurodegenerative diseases cause significant global disability and death, with a growing socioeconomic burden due to increasing life expectancy.
  • Current management strategies are largely palliative, as neurodegeneration progresses silently for decades before symptom onset.
  • Existing conceptual models are often retrospective, potentially confusing causes and consequences of neurodegeneration.

Purpose of the Study:

  • To propose innovative, paradigm-shifting views on the etiology of neurodegenerative diseases.
  • To enable timely prevention and treatment by exploring alternative etiological pathways.
  • To recommend future research avenues for a comprehensive understanding of neurodegeneration.

Main Methods:

  • Conceptual review outlining four alternative etiological perspectives on neurodegeneration.
  • Discussion of cardiovascular causes, cellular senescence, trophic interactions (including extracellular vesicles), and gut-brain axis dysbiosis.
  • Emphasis on an integrated, interdisciplinary research approach utilizing multimodal physiological and pathophysiological data.

Main Results:

  • Neurodegeneration may stem from primary cardiovascular issues disrupting brain-vasculature homeostasis.
  • Persistent senescent cells and metabolic diseases may contribute to neurodegeneration.
  • Altered trophic interactions and gut-brain axis dysbiosis, involving bacterial products, can lead to neuroinflammation and dysfunction.

Conclusions:

  • Rethinking the etiology of neurodegenerative diseases is crucial for developing effective treatments.
  • Exploring cardiovascular, cellular, trophic, and microbiome-related pathways offers new avenues for research.
  • An integrated, interdisciplinary approach is essential to overcome translational roadblocks and develop causative therapies.