Apolipoprotein E Polymorphism and Serum Concentration in Alzheimer's Disease in Nine European Centres: the ApoEurope Study

Abstract

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.

Parental history of Alzheimer disease associated with lower plasma apolipoprotein E levels

“…[2][3][4] Several studies have reported on the association between plasma apoE levels and AD or cognitive impairment, but with opposing results (table 1). [5][6][7][8][9][10] In some cross-sectional studies, plasma apoE levels were similar in patients with AD and controls, [6][7][8] whereas others found lower plasma apoE levels in patients with AD. 9 On the contrary, an earlier study reported higher plasma apoE levels in patients with AD.…”

Both Targeted Mass Spectrometry and Flow Sorting Analysis Methods Detected the Decreased Serum Apolipoprotein E Level in Alzheimer's Disease Patients

“…Within Europe, different frequencies of the 4 allele have been shown between the northern and southern regions (12). As a result, in European studies by the ApoEurope project, some countries failed to show 4 prevalence in AD, and other countries presented very low levels of serum ApoE in both control and AD populations, in contrast to other countries (23). Additionally, the ApoE 4 allele was not found to be associated with AD in less developed countries, restricting this association to only western countries (46,47).…”

“…Even though the ApoE 4 allele has been well known to indicate higher susceptibility to developing AD, their relation is still debated (23,46,47). In addition, other polymorphisms such as the promoter/enhancer region of the ApoE gene have been suggested to be associated with AD (26 -28).…”

“…It is also found in plaques and neurofibrillary tangles (20). Studies on the peripheral total ApoE level in AD generated various discrepancies, suggesting a decrease (23,49), increase (21), or no alteration (22,24,50) in AD. It has also been suggested that the serum ApoE level is determined by the ApoE polymorphism, with evidence that the 2 allele is linked to a high serum ApoE concentration and the 4 allele is associated with a low serum ApoE level (25,51,52).…”

“…In contrast, a Rotterdam study by Slooter et al reported no increase in the serum ApoE level in AD as determined via a colorimetric method (22). The ApoEurope project collected patient and control samples from nine centers in eight European countries and demonstrated both increased occurrence of the ApoE 4 allele and decreased serum ApoE levels in AD via ApoE quantification using an immunoturbidimetric method (23). This decrease of the ApoE concentration in AD was irrespective of the presence of the 4 allele, age, and gender.…”