Age-dependent change in the levels of Aβ40 and Aβ42 in cerebrospinal fluid from control subjects, and a decrease in the ratio of Aβ42 to Aβ40 level in cerebrospinal fluid from Alzheimer's disease patients

In order to address an age-dependent alteration in the concentration of beta-amyloid polypeptides (A beta s) within the central nervous system and its probable predisposition to amyloidgenesis in Alzheimer's disease (AD), we measured two species of soluble A beta s, A beta 40 and A beta 42, in cerebrospinal fluids (CSF) from randomly selected Japanese control subjects at various ages (n = 33) and then compared these data with those of probable Japanese AD patients (n = 23). CSF concentrations of A beta 40 and A beta 42 peptides were age-dependent (ANOVA, Bonferroni's multiple comparison; p < 0.01 and p <0.05, respectively) and were fewer in the infant than in adults. From mid-20, the A beta 40 concentrations were decreasing while A beta 42 were rather stable. A beta s in CSF from AD patients (n = 23), whose epsilon 4 allele frequency of the apolipoprotein E gene was higher than in controls (n = 83, p < 0.03), were not statistically different from those of age-matched controls (n = 13). A linear relationship was detected between the A beta 40 concentration and the Mini-Mental State Examination sco re (p < 0.05). The ratio of the A beta 42 to the A beta 40 level measured in the AD CSF samples was approximately 38% decreased compared to age-matched controls (p < 0.05). These data suggest that the physiological metabolism of soluble A beta s in the brain is regulated in an age-dependent manner, and that the ratio of A beta 42 to A beta 40 level in the CSF would be a useful marker for monitoring progression of AD. Copyright (C) 2000 S. Karger AG, Basel.