Cerebrospinal fluid beta-amyloid((1-42)) in Alzheimer disease - Differences between early- and late-onset Alzheimer disease and stability during the course of disease

Objectives: To study the diagnostic potential of the 42 amino acid form of beta-amyloid (beta-amyloid((1-42))) in cerebrospinal fluid (CSF) as a bioch emical marker for Alzheimer disease (AD), the intra-individual biological v ariation of CSF-beta-amyloid((1-42)) level in patients with AD, and the pos sible effects of differential binding between P-amyloid and apolipoprotein E isoforms on CSF-beta-amyloid((1-42)) levels. Design: A 20-month prospective follow-up study. Setting: Community population-based sample of consecutive patients with AD referred to the Pitea River Valley Hospital, Pitea, Sweden. Patients: Fifty-three patients with AD (mean +/- SD age, 71.4 +/- 7.4 years ) diagnosed according to the National Institute of Neurological and Communi cative Disorders and Stroke and Alzheimer's Disease and Related Disorders A ssociation criteria and 21 healthy, age-matched (mean +/- SD age, 68.8 +/- 8.0 years) control subjects. Main Outcome Measures: Cerebrospinal fluid beta-amyloid((1-42)) level-analy zed using enzyme-linked immunosorbent assay-and severity of dementia-analyz ed using the Mini-Mental State Examination. Results: Mean +/- SD levels of CSF-beta-amyloid((1-42)) were decreased (P<. 001) in patients with AD (709 +/- 304 pg/mL) compared with controls (1678 /- 436 pg/mL). Most patients with AD (49 [92%] of 53 patients) had reduced levels (<1130 pg/mL). A highly significant correlation (r = 0.90; P<.001) b etween baseline and 1-year follow-up CSF-beta-amyloid((1-42)) levels was fo und. There were no significant correlations between CSF-beta-amyloid((1-42) ) level and duration (r = -0.16) or severity (r = -0.02) of dementia. Low l evels were also found in patients with mild dementia (Mini-Mental State Exa mination score, >25). Conclusions: The sensitivity of CSF-beta-amyloid((1-42)) level as a diagnos tic marker for AD is high. The intraindividual biological variation in CSF- beta-amyloid((1-42)) level is low. Low CSF-beta-amyloid((1-42)) levels are also found in the earlier stages of dementia in patients with AD. These fin dings suggest that CSF-beta-amyloid((1-42)) analyses may be of value in the clinical diagnosis of AD, especially in the early course of the disease, w hen drug therapy may have the greatest potential of being effective but cli nical diagnosis is particularly difficult.