Neurodevelopmental origins of age-related neurodegenerative diseases.

Abstract

Alzheimer's disease-related dementia (ADRD) is a progressive neurodegenerative condition characterised by cognitive decline and overlapping pathological features. Despite advances in diagnostic tools and therapies, challenges persist due to limited efficacy, high costs, and the complexity of ADRD pathophysiology. Evidence suggests that ADRD arises from a lifelong interplay of genetic, lifestyle, and environmental factors, with recent findings indicating potential neurodevelopmental origins. Proteins implicated in neurodegeneration, such as amyloid and tau, may play critical roles in early nervous system development, whereas disruptions during critical periods, such as adolescence, may increase later-life susceptibility to ADRD. The global prevalence of ADRD is projected to reach 153 million by 2050, emphasising the urgent need for prevention strategies in addition to therapeutic interventions. Reframing ADRD as a neurodevelopmental condition with a delayed onset may provide alternative insights into its aetiology, paving the way for alternative innovative therapeutic and preventive approaches.