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Publication : Presenilin 1-related alterations in DNA integrity in a transgenic mouse model of Alzheimer's disease.

First Author  Michelsen KA Year  2010
Journal  Brain Res Volume  1316
Pages  139-44 PubMed ID  20034479
Mgi Jnum  J:158786 Mgi Id  MGI:4440420
Doi  10.1016/j.brainres.2009.12.033 Citation  Michelsen KA, et al. (2010) Presenilin 1-related alterations in DNA integrity in a transgenic mouse model of Alzheimer's disease. Brain Res 1316:139-44
abstractText  The present study tested the hypothesis that mutations in amyloid precursor protein (APP) and presenilin (PS) 1 result in alterations in the amount of nuclear (n) DNA repair and nDNA damage in neurons in vivo. To this end, the relative amount of nDNA repair was measured in 8-month-old transgenic mice expressing either human mutant APP (APP751(SL) mice), human mutant PS1 (PS1(M146L) mice) or both human mutant APP and PS1 (APP751(SL)/PS1(M146L) mice) with unscheduled DNA synthesis, and the relative amount of nDNA single strand breaks (SSB) with in situ nick translation. APP751(SL)/PS1(M146L) mice showed a significantly decreased relative amount of nDNA repair in pyramidal cells in hippocampal area CA1/2 compared to APP751(SL) mice. Furthermore, PS1(M146L) mice showed a significantly increased relative amount of nDNA SSB in both granule cells in the dentate gyrus and pyramidal cells in area CA1/2 compared to both APP751(SL) mice and APP751(SL)/PS1(M146L) mice. These results might indicate a previously unknown action of mutations in PS1 on DNA integrity, which might be involved in the pathophysiologic processes of mutant PS1 in Alzheimer's disease.
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