کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
331303 | 1433648 | 2008 | 10 صفحه PDF | دانلود رایگان |
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 knockin 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.
Journal: Neurobiology of Aging - Volume 29, Issue 3, March 2008, Pages 319–328