Gene dose of the epsilon 4 allele of apolipoprotein E and disease progression in sporadic late-onset Alzheimer's disease.
A strong association has been described in cross-sectional studies between the epsilon 4 allele of the apolipoprotein E and late-onset Alzheimer's disease (LOAD). This study addresses the relationship between disease progression and the epsilon 4 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 -/-, epsilon 4/-, and epsilon 4/epsilon 4 patients. The proportion of patients with fast progression decreased (p < or = 0.005) and with slow progression increased (p = 0.002) with increasing epsilon 4 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 epsilon 4 carriers and that this might at least partly account for the cross-sectional association between the epsilon 4 allele and LOAD.
Frisoni
G B
GB
Alzheimer's Disease Unit, Istituto S. Cuore-FBF, Brescia, Italy.
Govoni
S
S
Geroldi
C
C
Bianchetti
A
A
Calabresi
L
L
Franceschini
G
G
Trabucchi
M
M
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D010641:Phenotype
D001057:Apolipoproteins E