The influence of the apolipoprotein-E polymorphism in the lipid profile of Alzheimer's disease or vascular dementia patients

THESES

The influence of the apolipoprotein-E polymorphism in the lipid profile of alzheimer's disease or vascular dementia patients. (Abstract)^*. Dissertation. São José do Rio Preto, 2002.

Silvia Aparecida Soares

^{Address to correspondence}

The apolipoprotein E (apo E) plays an important role in the modulation of atherogenic lipoproteins and in the pathogenesis of Alzheimer's disease. Recognizing the association between these two functions would make early clinical intervention possible, with obvious benefits in terms of patient care.

This study aimed to assess the influence of the apo E genetic polymorphism in the lipid profile of late onset Alzheimer's disease (LAD) and vascular dementia (VD) patients and controls. The possibility that the apo E polymorphism could become a risk factor for dementia because of its influence on the lipid profile in those patients was investigated.

A total of one hundred and sixty-one subjects were studied (mean age 72 years) and divided into three groups: Group 1 (G1) = 63 patients with AD; Group 2 (G2) = 38 patients with VD; Group 3 (G3) = 60 individuals without clinical signs of these diseases. All patients were clinically assessed following standard protocol and guidelines (NINCDS-ADRA).

DNA was extracted from leukocytes by means of amplification of the apo E gene through polymerase chain reaction, and the products were submitted to enzymatic restriction with Hha I. Investigation of the lipid profile included measurement of the levels of triglycerides (TG), total cholesterol (TC), and cholesterol fractions of low density lipoprotein (LDLc), high density lipoprotein (HDLc) and very low density lipoprotein (VLDLc). All data were submitted to statistical analysis.

The frequency of e4 allele was significantly higher in AD (0.27) compared with controls (0.10; p= 0.004).The e3/e3 genotype was prevalent in all groups, mainly in G2 and G3 (71.0%; 73.3%, respectively). e4 genotypes had the highest incidence in G1 (47.6%), while e3/e3 genotype was more frequent in G3 (73.3%). Mean values of TC and LDLc in G2 for e3/e3 genotype were significantly higher specifically for e-/e4 (223.6± 57.7; 300.4±61.3 mg/dL, respectively) compared with G1 (161.3±38.7; 236.8±45.7 mg/dL, respectively) and G3 (142.7±29.2; 220.3±33.6 mg/dL, respectively). Mean TG levels in G2, independent of apo E genotypes, also showed a significant increase, compared to G1 and G3. Mean values of HDLc and VLDLc remained within the desirable range in all groups and genotypes, although in G2 the mean level of HDLc was significantly lower (36.9±12.9 mg/dL) compared to G1 (51.3±17.5 mg/dL) and G3 (51.5 ±14.1 mg/dL), exclusively for the e3/e3 genotype. Conversely, the prevalence of e-/e4 genotypes was significantly higher in AD patients with increased TC, LDLc and TG levels when compared to the control group. There was, however, no significant difference between AD and VD or between VD and the control group.

In conclusion, the incidence of the e4 allele and e-/e4 genotypes allows discrimination between AD patients and controls and characterizes e4 as a risk factor for AD. Its prevalence, however, does not differentiate VD patients from controls, which suggests that the apo E polymorphism plays a less significant role in VD than in AD. A higher incidence of e4 in AD patients with an altered lipid profile suggests that both factors play a role in the pathogenesis of the disease. The similarity between AD, VD and controls is indicative of the presence of other factors that might influence lipid metabolism besides the e4 allele in VD.

Keywords: apolipoprotein E, lipid profile, vascular dementia, Alzheimer's disease.

*

Estudo do polimorfismo genético da apolipoproteína E e sua influência no perfil lipídico em pacientes com demência (Resumo). Dissertação de Mestrado. Faculdade de Medicina de São José do Rio Preto- FAMERP (Área: Neurogeriatria). Orientadora: Dorotéia Rossi Silva Souza. Co-orientador: Waldir Antonio Tognola

Publication Dates

• Publication in this collection
  16 Apr 2003
• Date of issue
  Mar 2003