Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy

Debrah I. Boeras, Antoneta Granic, Jaya Padmanabhan, Nichole C. Crespo, Amyn M. Rojiani, Huntington Potter

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)319-328
Number of pages10
JournalNeurobiology of Aging
Issue number3
StatePublished - Mar 2008

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology


Dive into the research topics of 'Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy'. Together they form a unique fingerprint.

Cite this