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Cerebrospinal Fluid -Amyloid_(1-42) in Alzheimer Disease

Differences Between Early- and Late-Onset Alzheimer Disease and Stability During the Course of Disease

Niels Andreasen, MD; Camilla Hesse; Pia Davidsson, PhD; Lennart Minthon, MD, PhD; Anders Wallin, MD, PhD; Bengt Winblad, MD, PhD; Hugo Vanderstichele, PhD; Eugeen Vanmechelen, PhD; Kaj Blennow, MD, PhD

Arch Neurol. 1999;56:673-680.

Objectives  To study the diagnostic potential of the 42 amino acid form of -amyloid (-amyloid_(1-42)) in cerebrospinal fluid (CSF) as a biochemical marker for Alzheimer disease (AD), the intra-individual biological variation of CSF--amyloid_(1-42) level in patients with AD, and the possible effects of differential binding between -amyloid and apolipoprotein E isoforms on CSF--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 Piteå River Valley Hospital, Piteå, Sweden.

Patients  Fifty-three patients with AD (mean±SD age, 71.4±7.4 years) diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria and 21 healthy, age-matched (mean±SD age, 68.8±8.0 years) control subjects.

Main Outcome Measures  Cerebrospinal fluid -amyloid_(1-42) level—analyzed using enzyme-linked immunosorbent assay—and severity of dementia—analyzed using the Mini–Mental State Examination.

Results  Mean±SD levels of CSF--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) between baseline and 1-year follow-up CSF--amyloid_(1-42) levels was found. There were no significant correlations between CSF--amyloid_(1-42) level and duration (r=-0.16) or severity (r=-0.02) of dementia. Low levels were also found in patients with mild dementia (Mini–Mental State Examination score, >25).

Conclusions  The sensitivity of CSF--amyloid_(1-42) level as a diagnostic marker for AD is high. The intra-individual biological variation in CSF--amyloid_(1-42) level is low. Low CSF--amyloid_(1-42) levels are also found in the earlier stages of dementia in patients with AD. These findings suggest that CSF--amyloid_(1-42) analyses may be of value in the clinical diagnosis of AD, especially in the early course of the disease, when drug therapy may have the greatest potential of being effective but clinical diagnosis is particularly difficult.

From the Department of Rehabilitation, Piteå River Valley Hospital, Piteå (Dr Andreasen, the Units of Neurochemistry (Ms Hesse, and Drs Davidsson and Blennow) and Psychiatry (Dr Wallin), Department of Clinical Neuroscience, University of Göteborg, Sahlgren's University Hospital, Mölndal, the Department of Clinical Neuroscience, Neuropsychiatric Clinic, Malmö University Hospital, Malmö (Dr Minthon), and the Section of Geriatric Medicine, Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm (Dr Winblad), Sweden; and The Medical Research Council (Dr Blennow), Sweden; and Innogenetics, Ghent, Belgium (Drs Vanderstichele and Vanmechelen).

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