The levels of water-soluble and triton-soluble Aβ are increased in Alzheimer's disease brain

Although plaques composed of the amyloid beta-protein (A beta) are considered a defining feature of Alzheimer's disease (AD), they are also found in cognitively normal individuals and extensive evidence suggests that non-plaque, water-soluble forms of A beta may play a role in AD pathogenesis. However, the relationship between the levels of water-soluble A beta and the clinical severity of disease has never been investigated. Here, we present results of a pilot study designed to examine the levels of water-soluble forms of A beta in brains of individuals who died at clinically distinct stages of AD. Using a serial extraction method, we also investigated the levels of triton-soluble and formic acid-soluble A beta. We found that water-soluble and detergent-soluble A beta monomer and SDS-stable dimer were elevated in AD and that the levels of water soluble A beta did not increase with plaque pathology. These results support the notion that both water- and detergent-soluble A beta are important in AD and are not simply released from plaques by mechanical disruption. Moreover, the fact that the levels of water- and triton-soluble A beta were similar in very mild/mild AD and moderate/severe AD suggests that once a certain level of these species is attained, further accumulation is not necessary for the disease to progress. Consequently, therapeutic targeting of water-soluble A beta should best benefit individuals in earliest phases of the disease process. (C) 2012 Elsevier B.V. All rights reserved.