P4‐266: BETA‐AMYLOID oligomerization in Alzheimer's DISEASE DEMENTIA versus high pathology controls
Year: 2012
Type: article
Study design: Observational Study
Abstract: While amyloid-beta (Aβ) peptide deposition into insoluble plaques is a pathological hallmark of Alzheimer's disease, soluble oligomeric Aβ has been hypothesized to more directly underlie impaired learning and memory in dementia of the Alzheimer type. However, the lack of a sensitive, specific, and quantitative assay for Aβ oligomers has hampered rigorous tests of this hypothesis. We developed a plate-based fluorescence immunoassay for oligomeric Aβ sensitive to low pg/ml (<1 pM) concentrations of synthetic Aβ dimers. The assay uses the same Aβ-specific monoclonal antibody to both capture and detect Aβ. Sensitivity was enhanced using single molecule counting technology. The Aβ oligomer assay does not recognize monomeric Aβ, amyloid precursor protein, or other non-Aβ peptide oligomers. We tested frontal cortex lysates and cerebrospinal fluid from Alzheimer's patients and controls. Aβ oligomer concentrations in frontal cortex lysates from patients with dementia of the Alzheimer type were tightly correlated with the extent of Aβ plaque deposition (r=0.88), but this relationship was much weaker in non-demented patients with equivalent Aβ plaque pathology (r=0.30). The ratio of Aβ oligomer levels to plaque density fully distinguished demented from non-demented patients, with no overlap between groups. This finding was replicated in parietal cortex samples as well. Other Aβ and plaque measures did not distinguish demented from non-demented patients. Aβ oligomers were not detected in cerebrospinal fluid.
Source: Alzheimer s & Dementia
Institution: Washington University in St. Louis
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2007849331