From Early Adversity to Neurodegeneration: Stress Biomarkers as Predictive Signals for Lifespan Brain Health

Neurodegenerative diseases (NDs) represent a growing public health challenge worldwide. While their clinical manifestations typically emerge late in life, increasing evidence suggests that biological vulnerability may originate much earlier in life. Early childhood adversity, expressed through mechanisms of toxic stress and allostatic load, has been associated with chronic activation of the hypothalamic-pituitary-adrenal axis, mitochondrial dysfunction, oxidative stress, and persistent inflammation-molecular pathways that overlap with those implicated in neurodegeneration. This narrative review highlights recent advances linking early adversity with long-term brain health. It discusses stress-related biomarkers, such as hair cortisol, inflammatory cytokines, and epigenetic modifications, as potential early indicators of neurodegenerative risk. Remarkably, protective and benevolent childhood experiences may mitigate these biological trajectories, underscoring the role of resilience in shaping neurobiological outcomes. We argue that integrating pediatric cohorts, particularly in underrepresented regions such as Latin America, with longitudinal biomarker approaches and omics technologies offers a unique opportunity to identify early predictors and preventive strategies. Understanding neurodegeneration as a lifespan process opens new avenues for early intervention and public health policy.