The neurodegenerative decline of brain with ageing is an acute global demographic problem, as elderly population surges worldwide. However, ageing effect has not been systematically studied for cerebellum, an autonomous part of brain having motor, cognition, language and memory functions. By magnetic resonance investigation, we study brain-ageing process: 177 normal subjects, aged 20-80, with focus on cerebellum, the first larger-scale analysis as we know. We found that for whole brain, both grey-matter/GM and white-matter/WM) volumes deceases with ageing (by ~ 15%). Contrastingly, these volumes remain unexpectedly stable in ageing cerebellum, indicating neuroprotective ability. To estimate neuroplasticity resilience of brain-tissue, we evaluated GM/WM interrelationship, assessed by GM-volume/WM axial-diffusivity. During ageing, the GM/WM interrelationship is comparatively stable in cerebellum, while in whole brain this relationship is much variable (230% increase). We validated the cerebellar neuroprotective ability by epigenetic tissue ageing analysis (DNA-methylation). Ageing retardation-level (years) of brain-tissue follows the neurodevelopmental caudal-rostral-rhinal axis: cerebellum (maximum retardation/neuroprotection), occipital, frontal, and temporal region (minimum). We log-normally plotted ageing-retardation against phylogenic age of that brain region (million-years ago/MYA), and found linear relationship, implying a quantitative evolutionary behaviour, indicating cerebellum's phylogenic antiquity (Cambrian-era ~ 510MYA), which adapted the cerebellum to withstand degenerative damage. Finally, we investigated cerebellum's neurocognitive resilience, enabling focussed development of coordination, tool-making and language, while present-day humans evolutionarily progressed over Neanderthals. We found that humans show maximal cerebellar expansion and depth. Of seminal significance is that cerebellum is a unique paradoxical brain region with peak neuroprotective behaviour, and may have substantial therapeutic rehabilitative biotechnological implications in neurodegenerative disorders.
Keywords: Alzheimer’s disease; Epigenetic tissue ageing; Neurodegenerative disorder; Neurodevelopmental axis; Neurostimulation therapy.
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