Genetic association and linkage analysis of the apolipoprotein CII locus and familial Alzheimer's disease

We previously reported a genetic association between the 3.5 kb (F) Taq I restriction fragment length polymorphism allele of the apolipoprotein CII gene on chromosome 19 and familial Alzheimer's disease. Here, we report an additional analysis of this association performed on an expanded and better defined data set of 23 families with familial Alzheimer's disease. The F allele frequency in affected family members in the expanded set was 0.62 ± 0.06 (mean ± standard error, n = 51 subjects), which differed significantly from a frequency of 0.39 ± 0.02 (n = 226) for unrelated control subjects (Z = 3.75, p < 0.0002). These results are consistent with our previous findings and suggest an association between the F allele of apolipoprotein CII and familial Alzheimer's disease. When the apolipoprotein CII locus was tested for linkage to familial Alzheimer's disease, LOD scores summed for the complete group of families were negative and close linkage was excluded. Close linkage was also excluded for early‐onset families (mean onset age ≤ 60 years), but small positive LOD scores were obtained for late‐onset kindreds.

[1]  G. Schellenberg,et al.  APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease. , 1991, American journal of human genetics.

[2]  M. Pericak-Vance,et al.  Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. , 1991, American journal of human genetics.

[3]  S. Tsuji,et al.  Mis-sense mutation Val→Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease , 1991, The Lancet.

[4]  E M Wijsman,et al.  Linkage analysis of familial Alzheimer disease, using chromosome 21 markers. , 1991, American journal of human genetics.

[5]  M. Pericak-Vance,et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease , 1991, Nature.

[6]  I. Rainero,et al.  Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder , 1990, Nature.

[7]  S. M. Sumi,et al.  Familial dementia with PrP‐positive amyloid plaques , 1989, Neurology.

[8]  K. Kidd,et al.  Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms. , 1989, Cytogenetics and cell genetics.

[9]  J. Weber,et al.  Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. , 1989, American journal of human genetics.

[10]  S. M. Sumi,et al.  Phenotypic heterogeneity in familial alzheimer's disease: A study of 24 kindreds , 1989, Annals of neurology.

[11]  S. M. Sumi,et al.  Familial alzheimer's disease in american descendants of the volga germans: Probable genetic founder effect , 1988, Annals of neurology.

[12]  M. Boehnke,et al.  Allele frequency estimation from data on relatives. , 1991, American journal of human genetics.

[13]  T. Yasuda,et al.  Alpha-2-HS-glycoprotein polymorphism detected in human urine by isoelectric focusing and immunoblotting. , 1988, Human heredity.

[14]  K. Davis,et al.  Familial aggregation in Alzheimerʼs disease: comparison of risk among relatives of early- and late-onset cases, and among male and female relatives in successive generations , 1988 .

[15]  G. Assmann,et al.  Dimorphic markers for the human apolipoprotein CII gene locus. , 1987, Gene.

[16]  G. Schellenberg,et al.  Association of an apolipoprotein CII allele with familial dementia of the Alzheimer type. , 1987, Journal of neurogenetics.