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As part of the ApoEurope Project, apolipoprotein E (apo E) common polymorphism and serum concentration were determined in 489 Alzheimer's disease patients and 429 controls. Patients and controls were recruited through nine centres in eight European countries. Age, sex ratios and education levels of both case and control populations were similar, although discrete differences appeared between centres. The prevalence of the epsilon4 allele was higher in Alzheimer's disease than in controls (increased by 140%), while serum apo E concentration was lower by 11.2% (p<0.001). In addition, serum total cholesterol and triglyceride concentrations were lower in Alzheimer's disease (p<0.001), while that of apo Al was not affected. The decrease in serum apo E concentration was not accounted for by the epsilon4 allele, age or gender, suggesting that apo E concentration might represent an additional risk factor for Alzheimer's disease, complementary and independent of the epsilon4 allele. Further analysis will be aimed at determining whether the quantitative link between apo E concentration and Alzheimer's disease occurs through the effect of apo E genotype on lipid parameters or by other mechanisms.

The rate of sexual maturation among female Sprague-Dawley rats was measured in a variety of intraspecific social environments. It was found that females of this strain differ from at least one other strain of laboratory rat in that neither age at vaginal perforation nor age at first estrus was affected in Sprague-Dawley females by the presence or absence of male, regardless of his age or breeding history. Sizes of first litter among females who mated at their first estrus were compared with those among females who were first inseminated at older ages. On average, females bred at first estrus produced litters that contained more than 3 fewer pups than females mated at older ages. This observation suggests that female Sprague-Dawley rats do not attain full reproductive competence until sometime after the onset of puberty.

A collection of human B lymphoblastoid cell lines (LCLs) was used to map two genetic sequences for which polymorphism had not been identified: human prolactin (PRL) and tumor necrosis factor-beta (TNFB). The LCLs have overlapping deletions on chromosome 6p produced by gamma-irradiation of LCL 721. After using two chromosome 6p sequences for which LCL 721 is heterozygous to validate our scanning densitometry (SD) method for inferring gene copy number, SD was used to map TNFB and PRL. TNFB maps to the interval between the C4 complement and HLA-B loci within the MHC on chromosome 6p. PRL lies within the 6p21.3-6p22.2 interval distal to HLA-C. We found that LCL 721 is heterozygous for PRL DNA fragment lengths generated by HpaII but not MspI digestion, indicating that the two copies of PRL in LCL 721 are differentially methylated. This novel methylation RFLP was used to corroborate the region PRL assignment.

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