Alternative splicing and the aging brain in AfrAbia: New frontiers in dementia research

AfrAbia (Sub-Saharan Africa and Arab world), is undergoing a significant demographic shift characterized by increased longevity and rising dementia rates. Despite this, molecular insights into brain aging in these regions, especially in RNA processing pathways like alternative splicing (AS), are virtually absent. AS promotes transcriptomic and proteomic complexity and is pivotal for brain function, with its dysregulation connected to neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). However, current knowledge is overwhelmingly derived from Western populations, limiting global applicability. This perspective synthesizes the mechanisms and regulatory elements of AS, its role in aging and neurodegeneration, and emerging biomarkers and therapeutic strategies. Special attention is paid to ancestry-associated splicing variants and fluid biomarker development in AfrAbian cohorts. We argue for inclusive, population-specific molecular studies to bridge disparities in dementia diagnosis, treatment, and prevention.