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The Environment, Epigenetics and Amyloidogenesis

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Abstract

Alzheimer’s Disease (AD) is a progressive, irreversible neurodegenerative disease. Despite several genetic mutations (Haass et al., J. Biol. Chem. 269:17741–17748, 1994; Ancolio et al., Proc. Natl. Acad. Sci. USA 96:4119–4124, 1999; Munoz and Feldman, CMAJ 162:65–72, 2000; Gatz et al., Neurobiol. Aging 26:439–447, 2005) found in AD patients, more than 90% of AD cases are sporadic (Bertram and Tanzi, Hum. Mol. Genet. 13:R135–R141, 2004). Therefore, it is plausible that environmental exposure may be an etiologic factor in the pathogenesis of AD. The AD brain is characterized by extracellular beta-amyloid (Aβ) deposition and intracellular hyperphosphorylated tau protein. Our lab has demonstrated that developmental exposure of rodents to the heavy metal lead (Pb) increases APP (amyloid precursor protein) and Aβ production later in the aging brain (Basha et al., J. Neurosci. 25:823–829, 2005a). We also found elevations in the oxidative marker 8-oxo-dG in older animals that had been developmentally exposed to Pb (Bolin et al., FASEB J. 20:788–790, 2006) as well as promotion of amyloidogenic histopathology in primates. These findings indicate that early life experiences contribute to amyloidogenesis in old age perhaps through epigenetic pathways. Here we explore the role of epigenetics as the underlying mechanism that mediates this early exposure-latent pathogenesis with a special emphasis on alterations in the methylation profiles of CpG dinucleotides in the promoters of genes and their influence on both gene transcription and oxidative DNA damage.

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  1. Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, 02881, USA

    Jinfang Wu, Md. Riyaz Basha & Nasser H. Zawia

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  2. Md. Riyaz Basha
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  3. Nasser H. Zawia
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Correspondence to Nasser H. Zawia.

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Wu, J., Basha, M.R. & Zawia, N.H. The Environment, Epigenetics and Amyloidogenesis. J Mol Neurosci 34, 1–7 (2008). https://doi.org/10.1007/s12031-007-0009-4

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