PMID- 10408806
OWN - NLM
STAT- MEDLINE
DCOM- 19990824
LR  - 20071114
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 6
IP  - 3
DP  - 1999 Jun
TI  - Chromosome missegregation and trisomy 21 mosaicism in Alzheimer's disease.
PG  - 167-79
AB  - A connection between Alzheimer's disease (AD) and Down syndrome (trisomy 21) is 
      indicated by the fact that all Down syndrome individuals develop Alzheimer's 
      disease neuropathology by the 4th decade of life. Previous studies have examined 
      the frequency of aneuploidy and other chromosomal defects in cells from familial 
      Alzheimer's disease (FAD) patients, with varying results. To investigate the 
      possibility that a specific type of aneuploidy--trisomy 21 mosaicism--may 
      contribute to Alzheimer's disease, we used quantitative fluorescence in situ 
      hybridization to measure the number of trisomy 21 cells in primary fibroblast 
      cultures from AD and unaffected subjects. The 27 AD cultures, including 15 that 
      were derived from individuals carrying FAD mutations in presenilin 1 or 2, 
      exhibited a significant approximately twofold increase in the number of trisomy 
      21 cells compared to 13 control cultures. A small double-hybridization experiment 
      suggested that the aneuploidy in AD cells was not limited to chromosome 21 but 
      extended at least to chromosome 18 as well. In a parallel study, the endogenous 
      presenilin proteins in fibroblasts were localized to the centrosomes, the nuclear 
      envelope, and its associated interphase kinetochores. Together these results 
      indicate that the presenilin proteins may be involved in mitosis and that FAD 
      mutations in the presenilin genes may predispose to chromosome missegregation 
      (nondisjunction). The data reported here also suggest that trisomy 21 mosaicism 
      may contribute to other forms of AD that are not caused by a presenilin mutation.
FAU - Geller, L N
AU  - Geller LN
AD  - Fish & Richardson P.C., Boston, Massachusetts 02115, USA.
FAU - Potter, H
AU  - Potter H
LA  - eng
GR  - AG08084/AG/NIA NIH HHS/United States
GR  - AG09665/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Apolipoprotein E4)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Membrane Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (PSEN2 protein, human)
RN  - 0 (Presenilin-1)
RN  - 0 (Presenilin-2)
SB  - IM
MH  - Alleles
MH  - Alzheimer Disease/*genetics
MH  - Aneuploidy
MH  - Apolipoprotein E4
MH  - Apolipoproteins E/genetics
MH  - Cell Line
MH  - Centrosome/chemistry
MH  - *Chromosome Aberrations
MH  - *Chromosome Disorders
MH  - *Chromosome Segregation
MH  - Chromosomes, Human, Pair 1
MH  - Chromosomes, Human, Pair 14
MH  - Chromosomes, Human, Pair 18
MH  - *Chromosomes, Human, Pair 21
MH  - Down Syndrome/*genetics
MH  - Fibroblasts/cytology
MH  - Genotype
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interphase
MH  - Membrane Proteins/analysis/genetics
MH  - Mitosis
MH  - Mosaicism
MH  - Nuclear Envelope/chemistry
MH  - Presenilin-1
MH  - Presenilin-2
EDAT- 1999/07/17 00:00
MHDA- 1999/07/17 00:01
CRDT- 1999/07/17 00:00
PHST- 1999/07/17 00:00 [pubmed]
PHST- 1999/07/17 00:01 [medline]
PHST- 1999/07/17 00:00 [entrez]
AID - S0969-9961(99)90236-X [pii]
AID - 10.1006/nbdi.1999.0236 [doi]
PST - ppublish
SO  - Neurobiol Dis. 1999 Jun;6(3):167-79. doi: 10.1006/nbdi.1999.0236.