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Plasma and Cerebrospinal Fluid Levels of Amyloid Proteins 1-40 and 1-42 in Alzheimer Disease

Pankaj D. Mehta, PhD; Tuula Pirttilä, MD, PhD; Sangita P. Mehta, MS; Eugene A. Sersen, PhD; Paul S. Aisen, MD; Henryk M. Wisniewski, MD, PhD

Arch Neurol. 2000;57:100-105.

Background  In brains with AD, A is a major component of diffuse plaques. Previous reports showed that CSF A42 levels were lower in patients with AD than in controls. Although studies showed higher plasma A42 levels in familial AD, a recent report has indicated that plasma A42 levels were similar in a sporadic AD group and controls. However, no information is published on plasma A40 and A42 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 protein 1-40 (A40) and 1-42 (A42) 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 A40 and A42 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 A40 levels were higher in the AD group than in controls (P = .005), but there was substantial overlap; A42 levels were similar between the groups. Levels of A40 and A42 showed no association with sex or Mini-Mental State Examination scores. There was a significant relationship between age and A40 level in controls but not in the AD group. Levels of A40 were higher in patients with AD with the Apo E 4 allele than in controls (P<.01). Cerebrospinal fluid A40 levels were similar in the AD group and controls. However, A42 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 A40 levels are elevated in sporadic AD and influenced by Apo E genotype, measurement of plasma A40 levels is not useful to support the clinical diagnosis of AD. Lower levels of CSF A42 in the AD group are consistent with previous studies.

From the Departments of Immunology (Dr Mehta and Ms Mehta), Psychology (Dr Sersen), and Neuropathology (Dr Wisniewski), New York State Institute for Basic Research in Developmental Disabilities, Staten Island, and the Department of Psychiatry, Mount Sinai School of Medicine, New York (Dr Aisen), NY; and the Department of Neurology, Tampere University Hospital, Tampere, Finland (Dr Pirttilä). Dr Aisen is now with the Department of Neurology, Georgetown University Medical Center, Washington, DC.

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