Brain Aging: Influence of Early–Life Events on Late-Life Brain Disorders

Abstract

The prominent symptoms of Alzheimer’s disease (AD) include severe loss of memory, failure of cognition and reasoning, and overall deficit of other intellectual abilities. AD usually appears late in adult life, but when the disease initiates and how long the disease processes take to develop are presently unknown. To address this issue, the “Latent Early–life Associated Regulation” (LEARn) model has been proposed. This model explains the etiology of AD and integrates both the neuropathological features (e.g., amyloid-beta plaques and hyperphosphorylated tau tangles) and environmental conditions (e.g., dietary imbalance, metal exposure, and pestichemicals) associated with AD. As per the LEARn model, environmental agents could perturb gene regulation in a long–term fashion, beginning at early developmental stages, but these perturbations would not have pathological results until significantly later in life, if an additional perturbation were to occur. The LEARn model postulates latent expression of specific genes triggered at an early stage of life. The LEARn model operates via the regulatory region (promoter) of the gene, specifically through changes in methylation and oxidation status within the promoter of specific genes. Thus, the LEARn model unifies genetic and environmental risk factors to explain the etiology of the most common, sporadic form of AD. Finally, the possible medical remediation is discussed with reference to the relatively long term of latency under the LEARn model.