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 . 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.
Keywords: Alzheimer’s disease, cognitive function, amyloid hypothesis, APP, LOAD.
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