Long-Term Consequences of Perinatal Asphyxia in the Development of Alzheimer's Disease

Despite remarkable progress in medicine, perinatal asphyxia (PA) remains a significant clinical problem, and concerns regarding its long-term complications are increasingly being raised. Emerging evidence indicates that similar pathological pathways are activated following PA and during neurodegeneration in Alzheimer's disease (AD). These similarities involve various mechanisms, including alterations in AD-related proteins and their gene expression. Disturbances in neurotransmitter function can lead to excitotoxicity and cell death via necrosis and delayed apoptosis. Additionally, as observed in AD, dysregulation of autophagic processes has been reported. Pathological changes initiated by hypoxia in the newborn may trigger chronic neuroinflammation that persists long-term. Similarly, neuroinflammation plays a critical role in the pathogenesis of AD. Other common mechanisms include oxidative stress and mitochondrial dysfunction. Estrogens appear to have a protective effect in both PA and AD; however, ovaries exposed to PA may exhibit a reduced ovarian reserve, potentially diminishing neuroprotection later in life. Epigenetic modifications have also been proposed as a link between PA and AD. This review focuses on the changes that occur in the neonatal brain following PA, with particular emphasis on long-term consequences. We highlight common pathogenetic and causal pathways that may connect PA to the development of AD. Furthermore, we summarize key studies from the past 25 years addressing these topics and briefly discuss current research directions in the treatment of experimental and clinical PA.