title: The levels of water-soluble and triton-soluble Aβ are increased in Alzheimer's disease brain.
abstract: Although plaques composed of the amyloid β-protein (Aβ) 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 Aβ may play a role in AD pathogenesis. However, the relationship between the levels of water-soluble Aβ 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 Aβ 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 Aβ. We found that water-soluble and detergent-soluble Aβ monomer and SDS-stable dimer were elevated in AD and that the levels of water soluble Aβ did not increase with plaque pathology. These results support the notion that both water- and detergent-soluble Aβ 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 Aβ 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 Aβ should best benefit individuals in earliest phases of the disease process.
authors.affiliation: Laboratory for Neurodegenerative Research, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin 4, Ireland.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: McDonald
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: Lisa
authors.initials: L
authors.lastname: Taylor-Reinwald
authors.forename: David
authors.initials: D
authors.lastname: Holtzman
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Walsh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor