| First Author | Boeras DI | Year | 2008 |
| Journal | Neurobiol Aging | Volume | 29 |
| Issue | 3 | Pages | 319-28 |
| PubMed ID | 17169464 | Mgi Jnum | J:135054 |
| Mgi Id | MGI:3790295 | Doi | 10.1016/j.neurobiolaging.2006.10.027 |
| Citation | Boeras DI, et al. (2008) Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy. Neurobiol Aging 29(3):319-28 |
| abstractText | Mutations in the presenilin 1 gene cause most early onset familial Alzheimer's disease (FAD). Here, we report that a defect in the cell cycle - improper chromosome segregation - can be caused by abnormal presenilin function and therefore may contribute to AD pathogenesis. Specifically we find that either over-expression or FAD mutation in presenilin 1 (M146L and M146V) leads to chromosome missegregation and aneuploidy in vivo and in vitro: (1) Up to 20% of lymphocytes and neurons of FAD-PS-1 transgenic and knocking mice are aneuploid by metaphase chromosome analysis and in situ hybridization. (2) Transiently transfected human cells over-expressing normal or mutant PS-1 develop similar aneuploidy within 48 h, including trisomy 21. (3) Mitotic spindles in the PS-1 transfected cells contain abnormal microtubule arrays and lagging chromosomes. Several mechanisms by which chromosome missegregation induced by presenilin may contribute to Alzheimer's disease are discussed. |
