Soluble amyloid-beta buffering by plaques in Alzheimer disease dementia versus high-pathology controls
An unanswered question regarding Alzheimer disease dementia (ADD) is whether amyloid-beta (A{beta}) plaques sequester toxic soluble A{beta} species early in the pathological progression. We previously reported that the concentration of soluble A{beta} aggregates from patients with mild dementia was higher than soluble A{beta} aggregates from patients with modest A{beta} plaque burden but no dementia. The ratio of soluble A{beta} aggregate concentration to A{beta} plaque area fully distinguished these groups of patients. We hypothesized that initially plaques may serve as a reservoir or sink for toxic soluble A{beta} aggregates, sequestering them from other targets in the extracellular space and thereby preventing their toxicity. To initially test a generalized version of this hypothesis, we have performed binding assessments using biotinylated synthetic A{beta}1-42 peptide. A{beta}1-42-biotin peptide was incubated on unfixed frozen sections from non-demented high plaque pathology controls and patients with dementia of the Alzheimer type. The bound peptide was measured using ELISA and confocal microscopy. We observed no quantitative difference in A{beta} binding between the groups using either method. Further testing of the buffering hypothesis using various forms of synthetic and human derived soluble A{beta} aggregates will be required to definitively address the role of plaque buffering as it relates to ADD.