The relationship between apolipoprotein E4 and lipid metabolism is impaired in Alzheimer's disease

Background: Human apolipoprotein (Apo) E4 (ApoE4) is an important determina nt of lipid metabolism and cell-to-cell cholesterol transport. It is also a major genetic risk factor for both vascular disease and familial and spora dic late-onset Alzheimer's disease (AD). Since vascular pathology could dra matically reduce neuronal reserve capacity, a biological chain of events be tween ApoE4, hypercholesterolemia and AD has been postulated. The aim of th e present study is to explore the relationship between lipid metabolism and ApoE isoforms in a large series of elderly subjects in relation to the pre sence or absence of AD. Methods: Of 332 referrals to a neurology clinic spe cializing in memory disorders, 146 were given a diagnosis of AD (age, mean +/- SD 76 +/- 13.1 years, 64.4% women) according to DSM-IIIR criteria. One hundred and seventy-six subjects were included as controls (age 80 +/- 5.6 years, 58% women). The ApoE phenotype was determined by the isoelectrofocal ization method, cholesterol, triglycerides, phospholipids, ApoA and ApoB we re determined by routine chemistry. Findings: A significant association was observed between the E4 allele and AD (chi (2) = 13, p < 0.001) only below age 80. In the control group, cholesterol levels were found to be signific antly higher in men but not in women with an E4 allele (6.35 +/- 1.3 mmol/l ) as opposed to those without (5.8 +/- 1.2 mmol/l). ApoB levels were also f ound to be higher in the presence of ApoE4, with no gender effect. Within t he AD group no significant relationship was found between ApoE4 and cholest erol levels (mean 6.05 +/- 0.9 mmol/l in E4-AD subjects versus 5.8 +/- 1.21 mmol/l in non-ELF-AD subjects). Similar observations were made in relation to triglycerides and phospholipids. Interpretation: Our results demonstrat e the disappearance of the ApoE4-raising effect on serum cholesterol, trigl yceride and phospholipid levels in AD suggesting a more complex relationshi p between AD and lipid metabolism than has previously been supposed. This l ipid abnormality may further contribute to the progression of AD. Copyright (C) 2001 S. Karger AG, Basel.