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

Antibodies to amyloid β protein (Aβ) are present naturally or after Aβ 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 Aβ40 monomer and dimer, and the Aβ42 monomer weakly, but not with the Aβ42 dimer. TAPIR was even detected in samples from young normal subjects and young Tg2576 transgenic mice. Although the Aβ40 level and Aβ40/42 ratio increased, and Aβ42 was significantly decreased in plasma from AD groups when compared to controls, no significant correlations were revealed between plasma Aβ levels and TAPIR grading. Thus an immune response to Aβ40 and immune tolerance to Aβ42 occurred naturally in humans without a close relationship to the Aβ burden in the brain. Clarification of the mechanism of the immune response to Aβ42 is necessary for realization of an immunotherapy for AD.