How Biochemical Pathways for Disease May be Triggered by Early-Life Events

  • Debomoy K. Lahiri
  • Bryan Maloney
  • Nasser H. Zawia


Alzheimer’s disease (AD) is the most common form of dementia among the elderly and usually appears late in adult life. It is presently uncertain when process of this disease starts and how long these pathobiochemical processes take to develop. Therefore, we address the timing and nature of triggers that lead to AD. To explain the etiology of AD, we propose a “Latent Early-life Associated Regulation” (LEARn) model which postulates latent expression of specific genes triggered at the developmental stage of life. This model integrates both the neuropathological features (e.g., amyloid-loaded plaques and tau-laden tangles) and environmental conditions (e.g., diet, metal exposure, and hormones) associated with AD. In 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. The LEARn model operates through the regulatory region (promoter) of the gene, specifically through changes in methylation and oxidation status within the promoter of specific genes. The LEARn model combines genetic and environmental risk factors to explain the etiology of the most common, sporadic, form of AD.


LEARn Model Epigenetic Drift Concentrate Apple Juice Childhood Weight Gain Perturb Gene Expression 


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Debomoy K. Lahiri
    • 1
  • Bryan Maloney
  • Nasser H. Zawia
  1. 1.Department of Psychiatry and of Medical & Molecular Genetics MemberIndiana University School of Medicine Institute of Psychiatric ResearchIndianapolisUSA

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