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. |