Applying a systemic approach that extends beyond the brain to Alzheimer’s disease pathogenesis

Abstract

Traditional dementia research often isolates single aspects, biomarkers or symptoms, overlooking complex interactions shaping disease risk and progression. Lysosomal and mitochondrial dysfunction, reflecting systemic processes, may explain links between Alzheimer’s and metabolic, inflammatory, cardiovascular, ageing, genetic, environmental, and endocrine factors. Barnaghi et al. propose reframing Alzheimer's disease as a systemic disorder rooted in lysosomal and mitochondrial dysfunction, rather than solely a brain-confined condition. This whole-body perspective explains the links to metabolic, cardiovascular, and inflammatory comorbidities and highlights windows for early intervention.