Fractal dimension reveals cellular morphological changes as early biomarkers in neurodegenerative diseases: A narrative review

Fractal dimension has emerged as a powerful tool for capturing structural irregularities and self-similar patterns in biological tissues, providing crucial insights beyond traditional morphological assessments. It is a potentially powerful tool in the study of morphological changes in cells and tissues. Herein, we discuss the general principles of fractal dimension and its application in evaluating cellular changes, and then delve into its specific utility in neurodegenerative diseases, such as Alzheimer’s disease, multiple sclerosis, cerebral ischemia, and amyotrophic lateral sclerosis. We highlight studies involving diverse cell types—including astrocytes, oligodendrocytes, neurons, microglia, and Schwann cells—investigated in both animal models and clinical trials. This review examines the rapidly expanding significance of fractal dimension as a quantitative approach for characterizing complex cellular morphologies, with a particular focus on neurodegenerative diseases. Evidence indicates that alterations in fractal dimension are associated with underlying biochemical and molecular changes. Given the high heterogeneity of brain cells and the cellular alterations associated with neurodegenerative diseases, fractal dimension is emerging as a significant tool for disease diagnosis and prognosis. Therefore, this approach offers a deeper understanding of neurodegenerative disease progression by examining both cellular morphological changes and overall tissue-level transformations. Fractal dimension holds potential as a biomarker for early diagnosis and prognostic evaluation of neurodegenerative disorders.