GENE DOSE OF THE EPSILON-4 ALLELE OF APOLIPOPROTEIN-E AND DISEASE PROGRESSION IN SPORADIC LATE-ONSET ALZHEIMERS-DISEASE

A strong association has been described in cross-sectional studies between the ε4 allele of the apolipoprotein E and late-onset Alzheimer's disease (LOAD). This study addresses the relationship between disease progression and the ε4 allele in 62 sporadic LOAD (onset at age 70 and over) patients. Disease progression was estimated retrospectively with the Mini-Mental State Examination (MMSE) amounting to 4.7, 3.8, and 2.2 points per year (sex- adjusted test for trend: p = 0.01) and with the Clinical Dementia Rating (CDR) to 0.76, 0.67, and 0.42 units per year (p = 0.03) in -/-, ε4/-, and ε4/ε4 patients. The proportion of patients with fast progression decreased (p ≤ 0.005) and with slow progression increased (p = 0.002) with increasing ε4 gene dose. These findings were confirmed in a smaller sample of 28 patients for whom longitudinal assessments of MMSE were available and when nonlinear progression of the disease was accounted for in a stratified analysis. These data suggest that disease duration might be longer in ε4 carriers and that this might at least partly account for the cross-sectional association between the ε4 allele and LOAD.