Neurodegeneration in Sub-Saharan Africa: Intersections of Biological Ageing, Genomic Diversity and the Lifetime Exposome.

Neurodegenerative diseases are emerging as an important consequence of population ageing in sub-Saharan Africa (SSA), but their scientific relevance extends beyond a projected rise in case numbers. SSA combines exceptional human genomic diversity with marked heterogeneity in vascular and metabolic risk, infection, nutrition, occupational exposures, air pollution, and access to health care. This combination creates an underused setting in which to study why biological ageing produces neurodegeneration in some individuals but relative resilience in others. This review critically synthesises evidence on Alzheimer's disease and related dementias, Parkinson's disease, amyotrophic lateral sclerosis/frontotemporal degeneration, Huntington's disease and related disorders, focusing on the intersection between hallmarks of ageing, disease-specific proteinopathies, ancestry and the lifetime exposome. Age-associated loss of proteostasis, mitochondrial dysfunction, impaired autophagy, chronic inflammation, neurovascular injury and genomic/epigenomic instability provide a mechanistic scaffold on which genetic susceptibility and cumulative exposures may act. Yet African evidence remains dominated by cross-sectional clinical phenotyping; neuropathology, longitudinal biomarkers, multi-omics and measured environmental exposures remain sparse. Recent African-ancestry Parkinson's disease genomics and emerging plasma biomarker studies demonstrate that ancestry-inclusive molecular neuroscience is feasible and can generate findings not predictable from European-ancestry datasets. The next phase should therefore move beyond documenting underdiagnosis toward longitudinal, biologically anchored cohorts that integrate phenotype, genomics, blood biomarkers, neuroimaging, exposomics, digital measures and health-system outcomes. This review proposes a research framework centred on biological ageing, gene-environment interaction and resilience. Such work would improve the validity of prevention, diagnosis and therapeutic translation in African populations while contributing globally to a more complete biology of neurodegenerative ageing.