Do epigenetic pathways initiate late onset alzheimer disease (LOAD): Towards a new paradigm

Syed Waseem Bihaqi, Axel Schumacher, Bryan Maloney, Debomoy K. Lahiri, Nasser H. Zawia

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations


Late onset Alzheimer's disease (LOAD) is a non-familial, progressive neurodegenerative disease and the most prominent form of dementia in the elderly. Accumulating evidence suggests that LOAD not only results from the combined effects of variation in a number of genes and environmental factors, but also from epigenetic abnormalities such as histone modifications or DNA methylation. In comparison to monogenic diseases, LOAD exhibits numerous anomalies that suggest an epigenetic component in disease etiology. Evidence against a monogenic course and for an epigenetic component include: 1) the dominance of sporadic cases over familial ones and the low estimated concordance rates for monozygotic twins; 2) gender specific susceptibility and course of disease; 3) parent-of-origin effects, and late age of onset; 4) brain chromatin abnormalities, non-Mendelian inheritance patterns, and atypical levels of folate and homocysteine; and 5) monoallelic expression patterns of susceptibility genes [1]. The epigenome is particularly susceptible to deregulation during early embryonic and neonatal periods and thus disturbances during these periods can have latent lasting effects. The Latent Early-life Associated Regulation (LEARn) model attempts to explain these consequences from a brain specific point of view. In the present review we present the evidence that support the role of epigenetics in the development of AD and explore the potential pathways and mechanisms that may be involved.

Original languageEnglish (US)
Pages (from-to)574-588
Number of pages15
JournalCurrent Alzheimer research
Issue number5
StatePublished - Jun 1 2012


  • Alzheimer's disease
  • Amyloid hypothesis
  • APP
  • Cognitive function
  • LOAD

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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