Plasma and cerebrospinal fluid levels of amyloid β proteins 1-40 and 1-42 in Alzheimer disease

Background: In brains with AD, A beta is a major component of diffuse plaques. Previous reports showed that CSF A beta 42 levels were lower in patients with AD than in controls. Although studies showed higher plasma A beta 42 levels in familial AD, a recent report has indicated that plasma A beta 42 levels were similar in a sporadic AD group and controls. However, no information is published on plasma A beta 40 and A beta 42 levels in relation to Apo E genotype or severity of dementia in sporadic AD. Objective: To examine plasma and cerebrospinal fluid (CSF) levels of amyloid beta protein 1-40 (A beta 40) and 1-42 (A beta 42) levels in patients with probable Alzheimer disease (AD) and elderly nondemented control subjects in relation to the apolipoprotein E (Apo E) genotype and dementia severity. Setting: Two university medical centers. Patients and Methods: Levels of A beta 40 and A beta 42 were measured in plasma from 78 patients with AD and 61 controls and in CSF from 36 patients with AD and 29 controls by means of a sandwich enzyme-linked immunosorbent assay. Results: Mean plasma A beta 40 levels were higher in the AD group than in controls (P = .005), but there was substantial overlap; A beta 42 levels were similar between the groups. Levels of A beta 40 and A beta 42 showed no association with sex or Mini-Mental State Examination scores. There was a significant relationship between age and A beta 40 level in controls but not in the AD group. Levels of A beta 40 were higher in patients with AD with the Apo E epsilon 4 allele than in controls (P < .01). Cerebrospinal fluid A beta 40 levels were similar in the AD group and controls. However, A beta 42 levels were lower in the AD group than in controls (P < .001). The levels showed no association with severity of dementia. Conclusions: Although mean plasma A beta 40 levels are elevated in sporadic AD and influenced by Apo E genotype, measurement of plasma A beta 40 levels is not useful to support the clinical diagnosis of AD. Lower levels of CSF A beta 42 in the AD group are consistent with previous studies.