The enigma and implications of brain hemispheric asymmetry in neurodegenerative diseases

Abstract

The lateralization of the human brain may provide clues into the pathogenesis and progression of neurodegenerative diseases. Though differing in their presentation and underlying pathologies, neurodegenerative diseases are all devastating and share an intriguing theme of asymmetrical pathology and clinical symptoms. Parkinson’s disease, with its distinctive onset of motor symptoms on one side of the body, stands out in this regard, but a review of the literature reveals asymmetries in several other neurodegenerative diseases. Here we review the lateralization of the structure and function of the healthy human brain and the common genetic and epigenetic patterns contributing to the development of asymmetry in health and disease. We specifically examine the role of asymmetry in Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, and interrogate whether these imbalances may reveal meaningful clues about the origins of these diseases. We also propose several hypotheses for how lateralization may contribute to the distinctive and enigmatic features of asymmetry in neurodegenerative diseases, suggesting a role for asymmetry in the choroid plexus, neurochemistry, protein distribution, brain connectivity, and the vagus nerve. Finally, we suggest how future studies may reveal novel insights into these diseases through the lens of asymmetry.

Brain Asymmetry: Towards an Asymmetrical Neurovisceral Integration

“…Lubben et al [63] review the asymmetric nature of neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis or amyotrophic lateral sclerosis, highlighting the greater prevalence of the left hemisphere at the origin of all of these diseases. The authors suggest that the brain already develops with innate differences between both hemispheres, which implies that one of them is more vulnerable, causing the onset of the pathology to precipitate earlier and more easily.…”

Association of Outdoor Ambient Fine Particulate Matter With Intracellular White Matter Microstructural Properties Among Children

“… 59 A previous study 58 of asymmetry in neurologic disorders suggests that typical asymmetries develop between the hemispheres, which may ultimately result in greater hemispheric differences in vulnerability to brain pathologic conditions. A previous study 58 suggests that brain asymmetries occur via differences in functional genetic pathways of microtubule regulation, neurogenesis, and axonogenesis, which are involved in neuronal development and organization and the manifestation of hemispheric differences in gene expression. Thus, these asymmetries in brain structure and function may contribute to the hemisphere-specific patterns observed in this study.…”

“…Although the exact mechanisms underlying central nervous system asymmetries remain unknown, 58 structural and functional differences have been noted between the 2 cerebral hemispheres at the macroscopic, microstructural, and molecular levels. 59 A previous study 58 of asymmetry in neurologic disorders suggests that typical asymmetries develop between the hemispheres, which may ultimately result in greater hemispheric differences in vulnerability to brain pathologic conditions.…”

Asymmetric Interaction of Neuropeptidase Activities between Cortico-Limbic Structures, Plasma and Cardiovascular Function after Unilateral Dopamine Depletions of the Nigrostriatal System

“…Therefore, these results would be in agreement with what was observed in left brain injuries and brain pathologies that affect mainly the left hemisphere in some periods of its evolution [ 12 ]. In neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis or amyotrophic lateral sclerosis, which manifest brain asymmetry, there is predominantly a greater involvement of the left hemisphere [ 25 ]. More severe sensory–motor and cognitive problems were produced after accidents involving the left hemisphere than those produced in the right one [ 26 ].…”