PMID- 9007102
OWN - NLM
STAT- MEDLINE
DCOM- 19970213
LR  - 20220330
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 40
IP  - 6
DP  - 1996 Dec
TI  - Wide range in age of onset for chromosome 1--related familial Alzheimer's 
      disease.
PG  - 932-6
AB  - Mutations in three different genes on chromosomes 1, 14, and 21 cause autosomal 
      dominant forms of familial Alzheimer's disease (FAD). Most result in an 
      early-onset phenotype. However, several kindreds of Volga German ancestry have 
      the same chromosome 1 gene mutation and demonstrate a relatively older mean age 
      of onset and include individuals with late age of onset. In these families, the 
      mean age of onset is 54.9 +/- 8.4 years (range, 40-75 years), mean age at death 
      is 65.9 +/- 10.2 years (range, 43-88 years), and mean disease duration is 11.3 
      +/- 4.6 years (range, 5-23 years). This contrasts with a group of 7 families with 
      chromosome 14 mutations in which the mean age of onset is 44.8 +/- 4.8 years 
      (range, 30-55 years), mean age at death is 52.6 +/- 5.7 years (range, 39-65 
      years), and mean disease duration is 7.6 +/- 3.2 years (range, 2-17 years). (All 
      means are significantly different in the 2 groups of families, p < 0.005.) In the 
      chromosome 1 families, 7 persons (16%) had an age of onset at or older than 65 
      years and 22 (54%) survived to age 65 or older versus none in the chromosome 14 
      families. An example of probable nonpenetrance of disease at age 89 was also 
      found in a chromosome 1 kindred. It is concluded that, unlike the chromosome 14 
      gene, mutations in the chromosome 1 FAD gene may result in individuals with a 
      late age of onset overlapping with the more common sporadic form of the disease 
      occurring in the general population. In light of the great variability in age of 
      onset in persons with identical mutations, study of the genetic and environmental 
      factors contributing to delayed onset of disease in chromosomal 1 FAD kindreds 
      will be an important area for further investigation. Apolipoprotein E genotype 
      may be one such factor that plays a partial role in this variability.
FAU - Bird, T D
AU  - Bird TD
AD  - Department of Neurology, VA Medical Center, University of Washington Medical 
      School, Seattle, USA.
FAU - Levy-Lahad, E
AU  - Levy-Lahad E
FAU - Poorkaj, P
AU  - Poorkaj P
FAU - Sharma, V
AU  - Sharma V
FAU - Nemens, E
AU  - Nemens E
FAU - Lahad, A
AU  - Lahad A
FAU - Lampe, T H
AU  - Lampe TH
FAU - Schellenberg, G D
AU  - Schellenberg GD
LA  - eng
GR  - AG0513C/AG/NIA NIH HHS/United States
GR  - R01-AG11762/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (Apolipoproteins E)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Alzheimer Disease/ethnology/*genetics
MH  - Apolipoproteins E/genetics
MH  - *Chromosomes, Human, Pair 1
MH  - Chromosomes, Human, Pair 14
MH  - Chromosomes, Human, Pair 21
MH  - Ethnicity
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
EDAT- 1996/12/01 00:00
MHDA- 1996/12/01 00:01
CRDT- 1996/12/01 00:00
PHST- 1996/12/01 00:00 [pubmed]
PHST- 1996/12/01 00:01 [medline]
PHST- 1996/12/01 00:00 [entrez]
AID - 10.1002/ana.410400619 [doi]
PST - ppublish
SO  - Ann Neurol. 1996 Dec;40(6):932-6. doi: 10.1002/ana.410400619.