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S4‐03‐03: The “LEARn” (Latent Early‐life Associated Regulation) model may explain the etiology of sporadic cases of Alzheimer's disease
Author(s) -
Lahiri Debomoy K.,
Maloney Bryan,
Ray Balmiki,
Rogers Jack T.,
Zawia Nasser
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.501
Subject(s) - disease , gene , somatic cell , psychology , phenotype , effector , neuroscience , environmental enrichment , biology , genetics , microbiology and biotechnology , medicine
markers of DNA methylation was determined immunohistochemically. To develop quantitative data, integrated fluorescence intensities of immunoreactivity for 5-methylcytosine were recorded for nuclei of DAPI-and neuron specific enolase positive cells from coded slides. These data were evaluated by two-tailed t-test. Results: In the AD twin, decreased immunoreactivity for all markers was readily apparent. Similar results were obtained in the pathologically-vulnerable superior frontal gyrus, as well as with additional members of the MeCP1 complex. By two-tailed t-test, all markers exhibited highly significant (P < 0.0001) decrements in immunoreactivity in the AD twin compared to the ND twin. To show that the results obtained in cortex were not due to differences in tissue handling, storage time, or quality, DNA methylation markers were also evaluated in cerebellum. Cerebella of the twins exhibited virtually identical staining patterns and intensity for all the methylation markers examined. Conclusions: The present findings indicate that epigenetic mechanisms may provide a molecular basis for the effect of life events on AD risk. More specifically, they may provide a rationale for the consistent epidemiologic and neuropathologic association of AD with homocysteine elevation and folate deficiencies, since folate ultimately provides the methyl group for DNA methylation. Maintaining adequate dietary folate (and B12) or increasing S-adenosylmethionine levels might therefore be useful, inexpensive strategies to decrease risk for AD.