Plasma antibodies to Aβ40 and Aβ42 in patients with Alzheimer's disease and normal controls

Antibodies to amyloid beta protein (A beta) are present naturally or after A beta vaccine therapy in human plasma. To clarify their clinical role, we examined plasma samples from 113 patients with Alzheimer's disease (AD) and 205 normal controls using the tissue amyloid plaque immunoreactivity (TAPIR) assay. A high positive rate of TAPIR was revealed in AD (45.1%) and age-matched controls (41.2%), however, no significance was observed. No significant difference was observed in the MMS score or disease duration between TAPIR-positive and negative samples. TAPIR-positive plasma reacted with the A beta 40 monomer and dimer, and the A beta 42 monomer weakly, but not with the A beta 42 dimer. TAPIR was even detected in samples from young normal subjects and young Tg2576 transgenic mice. Although the A beta 40 level and A beta 40/42 ratio increased, and A beta 42 was significantly decreased in plasma from AD groups when compared to controls, no significant correlations were revealed between plasma A beta levels and TAPIR grading. Thus an immune response to A beta 40 and immune tolerance to A beta 42 occurred naturally in humans without a close relationship to the A beta burden in the brain. Clarification of the mechanism of the immune response to A beta 42 is necessary for realization of an immunotherapy for AD. (C) 2008 Elseveir B.V. All rights reserved.