title: Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease.
abstract: We previously observed low level mosaicism (2-4% normal cells) in phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) in 29% of a small group of elderly persons with Down syndrome (DS). An analysis of cytogenetic data on 154 trisomy 21 cases (age 1 day to 68 years) showed that the proportion of diploid cells in such cultures significantly increased (P < 0.005) with advancing age. Thus, the "occult" mosaicism in PBL of the elderly persons with DS is likely due to the accumulation of cells that have lost a chromosome 21. A consequence of chromosome 21 loss could be uniparental disomy of the 2n cells, a factor that might have significant biological consequences if some chromosome 21 genes are imprinted. Loss of a chromosome 21 from trisomic cells might result in tissue-specific mosaicism and "classical" mosaicism in different age groups. Chromosome 21 loss might also be relevant to the development of Alzheimer-type dementia in DS and in the general population.
authors.affiliation: Surrey Place Centre, Toronto, Ontario, Canada.
authors.forename: M E
authors.initials: ME
authors.lastname: Percy
authors.forename: V D
authors.initials: VD
authors.lastname: Markovic
authors.forename: A J
authors.initials: AJ
authors.lastname: Dalton
authors.forename: D R
authors.initials: DR
authors.lastname: McLachlan
authors.forename: J M
authors.initials: JM
authors.lastname: Berg
authors.forename: A C
authors.initials: AC
authors.lastname: Rusk
authors.forename: M J
authors.initials: MJ
authors.lastname: Somerville
authors.forename: B
authors.initials: B
authors.lastname: Chodakowski
authors.forename: D F
authors.initials: DF
authors.lastname: Andrews
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics; D000782:Aneuploidy; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009030:Mosaicism